Subsequent Vaccination Research Articles

Severe Multisystem Inflammatory Symptoms in 2 Adults after Short Interval between COVID-19 and Subsequent Vaccination.

We observed multisystem inflammatory syndrome in 2 older adults in the United States who had received mRNA coronavirus disease vaccine soon after natural infection. We identified 5 similar cases from the Vaccine Adverse Events Reporting System. The timing of vaccination soon after natural infection might have an adverse effect on the occurrence of vaccine-related systemic inflammatory disorders.

Spike BATTLE: Simultaneous evaluation of antigen-specific B and T lymphocytes following natural SARS-CoV-2 infection and subsequent mRNA vaccination

Abstract The development of effective vaccines and therapies against viral diseases requires reliable approaches for assessing durable immunological memory. Although a wealth of information is available from peripheral blood mononuclear cell samples, Conventional methods for quantifying and phenotyping antigen-specific lymphocytes can rapidly deplete irreplaceable specimens. This is due to the fact that antigen-specific T and B cells have historically been analyzed in independent assays each requiring millions of cells. A technique that facilitates the simultaneous detection of antigen-specific T and B cells would allow for more thorough immune profiling with significantly reduced sample requirements. To this end, we developed the B And T cell Tandem Lymphocyte Evaluation (BATTLE) assay, which allows for the simultaneous identification of SARS-CoV-2 Spike reactive T and B cells using an optimized Activation Induced Marker (AIM) T cell assay and a dual-color B cell antigen probes. Using this assay, we demonstrate that antigen-specific B and T cell subsets can be identified simultaneously using conventional flow cytometry platforms and provide insight into the differential effects of mRNA vaccination on B and T cell populations following natural SARS-CoV-2 infection. While spike-specific B cell and CD8+ T cell responses were higher following mRNA vaccination than natural infection alone, the quantity of CD4+ T cells recognizing spike was enhanced only in subjects with low responses to natural infection. Our findings suggest divergent patterns of B and T cell subset mobilization with repeated antigen encounter and highlight the utility of examining these populations in concert. Supported by the State of New York.

Towards a new model of global health justice: the case of COVID-19 vaccines

This paper questions an exclusively state-centred framing of global health justice and proposes a multilateral alternative. Using the distribution of COVID-19 vaccines to illustrate, we bring to light a broad...

Carrier Proteins Facilitate the Generation of Antipolysaccharide Immunity via Multiple Mechanisms.

ABSTRACTCapsular polysaccharides (CPSs) are important antigenic targets against bacterial infections. As T-independent antigens, however, CPSs elicit short-lived immune responses in adults and are poorly immunogenic in young children. Coupling CPS with protein carriers enhances anti-CPS responses and generates long-lasting immune memory. However, the mechanisms whereby carrier proteins accomplish this are not fully understood. Here, we dissect different mechanisms whereby carrier proteins enhance anti-CPS immunity. We show how coupling CPS with protein carriers modifies the interaction of CPS with antigen-presenting cells, enables a dual-activation mechanism for CPS-specific B cells via interaction with CPS- or carrier-specific T helper cells, and potentiates the recall of anti-CPS responses by engaging memory T helper cells during subsequent vaccination or bacterial exposure. Our findings provide new insights into the immunological basis of carrier-mediated anti-CPS immunity and may help in the design of more effective CPS-based vaccines.

The impact of pausing the Oxford-AstraZeneca COVID-19 vaccine on uptake in Europe: a difference-in-differences analysis.

BackgroundSeveral countries paused their rollouts of the Oxford-AstraZeneca coronavirus disease-19 (COVID-19) vaccine in mid-March 2021 due to concerns about vaccine-induced thrombosis and thrombocytopenia. Many warned that this risked damaging public confidence during a critical period of pandemic response. This study investigated whether the pause in the use of the Oxford-AstraZeneca vaccine had an impact on subsequent vaccine uptake in European countries.MethodsWe used a difference-in-differences approach capitalizing on the fact that some countries halted their rollouts whilst others did not. A longitudinal panel was constructed for European Economic Area countries spanning 15 weeks in early 2021. Media reports were used to identify countries that paused the Oxford-AstraZeneca vaccine and the timing of this. Data on vaccine uptake were available through the European Centre for Disease Control and Prevention COVID-19 Vaccine Tracker. Difference-in-differences linear regression models controlled for key confounders that could influence vaccine uptake, and country and week fixed effects. Further models and robustness checks were performed.ResultsThe panel included 28 countries, with 19 in the intervention group and 9 in the control group. Pausing the Oxford-AstraZeneca vaccine was associated with a 0.52% decrease in uptake for the first dose of a COVID-19 vaccine and a 1.49% decrease in the uptake for both doses, comparing countries that paused to those that did not. These estimates are not statistically significant (P = 0.86 and 0.39, respectively). For the Oxford-AstraZeneca vaccine only, the pause was associated with a 0.56% increase in uptake for the first dose and a 0.07% decrease in uptake for both doses. These estimates are also not statistically significant (P = 0.56 and 0.51, respectively). All our findings are robust to sensitivity analyses.ConclusionsAs new COVID-19 vaccines emerge, regulators should be cautious to deviate from usual protocols if further investigation on clinical or epidemiological grounds is warranted.

Severe Isolated Cardiomyopathy Requiring Heart Transplant Following COVID-19 Infection and Subsequent Vaccination

IntroductionCardiomyopathy is a known complication associated with COVID-19, and 7% of all COVID-19 related deaths are thought to be due to myocarditis. There is also growing evidence for COVID-19 vaccine-related myocarditis. We present the first case of a patient with severe isolated cardiomyopathy requiring heart transplant after both COVID-19 infection and vaccination.Case ReportA 58-year-old male with no prior medical history was diagnosed with COVID-19 infection in December 2020 without hospitalization. He experienced declining symptoms over the next 7 months and completed COVID-19 vaccination in July. On 8/10/2021, he presented to the emergency room with worsening exertional dyspnea and orthopnea. Initial labs revealed elevated NT-proBNP (1,701 pg/mL) and high-sensitivity cardiac troponin-T (45 ng/L). Transthoracic echocardiography revealed reduced left ventricular (LV) ejection fraction at 15% and LV end-diastolic diameter at 5.6 cm. Coronaries were clear. Cardiac MRI (cMR) is depicted in Figure 1. He was managed with an Impella device and dobutamine but failed weaning from this cardiac support. He was listed for transplant as UNOS Status 2 and underwent successful OHT on 9/19/2021.SummaryAcute myocardial injury is known to be a frequent complication during the COVID-19 course, but it is not known to require advanced therapies. There is only one other case from France that describes a patient bridged with temporary mechanical support to OHT following COVID-19 induced cardiomyopathy. In both cases, cMR revealed similar late gadolinium enhancement (LGE) patterns. The cases differ as our patient experienced Long COVID symptoms over 8 months after diagnosis and was vaccinated while the French report describes a patient who was diagnosed with COVID-19, experienced end-stage heart failure and underwent transplant all within 11 days. This case contributes to the lacunae in data in the era of COVID-19 and its vaccines.

Efficacy of vaccination and previous infection against the Omicron BA.1 variant in Syrian hamsters.

The emergence of the SARS-CoV-2 Omicron (B.1.1.529) variant with a surprising number of spike mutations raises concerns about reduced sensitivity of this virus to antibody neutralization and subsequent vaccine breakthrough infections. Here, we infect Moderna mRNA-vaccinated or previously infected hamsters with the Omicron BA.1 variant. While the Moderna mRNA vaccine reduces viral loads in the respiratory tissues upon challenge with an early S-614G isolate, the vaccine efficacy is not as pronounced after infection with the Omicron variant. Previous infection with the early SARS-CoV-2 isolate prevents replication after rechallenge with either virus in the lungs of previously infected hamsters, but the Omicron variant replicates efficiently in nasal turbinate tissue. These results experimentally demonstrate in an animal model that the antigenic changes in the Omicron variant are responsible for vaccine breakthrough and re-infection.

Dynamic assessment of the COVID-19 vaccine acceptance leveraging social media data

Vaccination is the most effective way to provide long-lasting immunity against viral infection; thus, rapid assessment of vaccine acceptance is a pressing challenge for health authorities. Prior studies have applied survey techniques to investigate vaccine acceptance, but these may be slow and expensive. This study investigates 29 million vaccine-related tweets from August 8, 2020 to April 19, 2021 and proposes a social media-based approach that derives a vaccine acceptance index (VAI) to quantify Twitter users’ opinions on COVID-19 vaccination. This index is calculated based on opinion classifications identified with the aid of natural language processing techniques and provides a quantitative metric to indicate the level of vaccine acceptance across different geographic scales in the U.S. The VAI is easily calculated from the number of positive and negative Tweets posted by a specific users and groups of users, it can be compiled for regions such a counties or states to provide geospatial information, and it can be tracked over time to assess changes in vaccine acceptance as related to trends in the media and politics. At the national level, it showed that the VAI moved from negative to positive in 2020 and maintained steady after January 2021. Through exploratory analysis of state- and county-level data, reliable assessments of VAI against subsequent vaccination rates could be made for counties with at least 30 users. The paper discusses information characteristics that enable consistent estimation of VAI. The findings support the use of social media to understand opinions and to offer a timely and cost-effective way to assess vaccine acceptance.

Neutralisation sensitivity of the SARS-CoV-2 omicron (B.1.1.529) variant: a cross-sectional study

BackgroundThe SARS-CoV-2 omicron (B.1.1.529) variant, which was first identified in November, 2021, spread rapidly in many countries, with a spike protein highly diverged from previously known variants, and raised concerns that this variant might evade neutralising antibody responses. We therefore aimed to characterise the sensitivity of the omicron variant to neutralisation.MethodsFor this cross-sectional study, we cloned the sequence encoding the omicron spike protein from a diagnostic sample to establish an omicron pseudotyped virus neutralisation assay. We quantified the neutralising antibody ID50 (the reciprocal dilution that produces 50% inhibition) against the omicron spike protein, and the fold-change in ID50 relative to the spike of wild-type SARS-CoV-2 (ie, the pandemic founder variant), for one convalescent reference plasma pool (WHO International Standard for anti-SARS-CoV-2 immunoglobulin [20/136]), three reference serum pools from vaccinated individuals, and two cohorts from Stockholm, Sweden: one comprising previously infected hospital workers (17 sampled in November, 2021, after vaccine rollout and nine in June or July, 2020, before vaccination) and one comprising serum from 40 randomly sampled blood donors donated during week 48 (Nov 29–Dec 5) of 2021. Furthermore, we assessed the neutralisation of omicron by five clinically relevant monoclonal antibodies (mAbs).FindingsNeutralising antibody responses in reference sample pools sampled shortly after infection or vaccination were substantially less potent against the omicron variant than against wild-type SARS-CoV-2 (seven-fold to 42-fold reduction in ID50 titres). Similarly, for sera obtained before vaccination in 2020 from a cohort of convalescent hospital workers, neutralisation of the omicron variant was low to undetectable (all ID50 titres <20). However, in serum samples obtained in 2021 from two cohorts in Stockholm, substantial cross-neutralisation of the omicron variant was observed. Sera from 17 hospital workers after infection and subsequent vaccination had a reduction in average potency of only five-fold relative to wild-type SARS-CoV-2 (geometric mean ID50 titre 495 vs 105), and two donors had no reduction in potency. A similar pattern was observed in randomly sampled blood donors (n=40), who had an eight-fold reduction in average potency against the omicron variant compared with wild-type SARS-CoV-2 (geometric mean ID50 titre 369 vs 45). We found that the omicron variant was resistant to neutralisation (50% inhibitory concentration [IC50] >10 μg/mL) by mAbs casirivimab (REGN-10933), imdevimab (REGN-10987), etesevimab (Ly-CoV016), and bamlanivimab (Ly-CoV555), which form part of antibody combinations used in the clinic to treat COVID-19. However, S309, the parent of sotrovimab, retained most of its activity, with only an approximately two-fold reduction in potency against the omicron variant compared with ancestral D614G SARS-CoV-2 (IC50 0·1–0·2 μg/mL).InterpretationThese data highlight the extensive, but incomplete, evasion of neutralising antibody responses by the omicron variant, and suggest that boosting with licensed vaccines might be sufficient to raise neutralising antibody titres to protective levels.FundingEuropean Union Horizon 2020 research and innovation programme, European and Developing Countries Clinical Trials Partnership, SciLifeLab, and the Erling-Persson Foundation.

Identification of dominant conformational epitopes from the whole structure of the proprotein convertase subtilisin/kexin type 9

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a negative regulator of LDLR, has emerged as an important target for the treatment of hypercholesterolemic cardiovascular disease, and monoclonal antibodies alirocumab and evolocumab against it have been widely used in clinical practice. The vaccine research of PCSK9 is considered a promising option for the long-term treatment and prevention of cardiovascular disease, but progress has been slow. The selection of safe and effective epitopes is one of the key steps in vaccine development. In this study, we designed a phage display library of cascaded peptides for affinity screening with two antibody drugs, and found that the two peptides PC3 and PS6, which are adjacent to each other in protein spatial structure, both have superior binding activity to the screening antibodies. We performed in vitro recombination design on the dominant sequences, and obtained recombinant sequences that can respond to the dominant conformational epitope of PCSK9, which provides a meaningful reference for epitope selection in subsequent PCSK9 vaccine development.

India’s COVID-19 vaccination policy-an analysis of problem, politics and policy

PurposeThe article aims to critically examine India's COVID-19 vaccination policy by analyzing the problem, politics and policy developed during the pandemic. The article would help the policy-makers and healthcare administrators to understand the situation in a holistic manner.Design/methodology/approachThe article employs Kingdon's multiple streams framework, which separately analyzes the problem at hand, the politics that are at work and the policy which is being developed when the problem and politics streams are activated. Directed approach to content analysis is adopted in this article.FindingsThe article provides a holistic overview of vaccine development and the vaccination policy during the COVID-19 pandemic in India.Practical implicationsThe analysis would help policy-makers and healthcare administrators to have a bird's-eye view of the COVID-19 vaccine development and the vaccination drive.Originality/valueThe article is a macro-level analysis of an extremely important situation of COVID-19 vaccine development and the subsequent vaccination drive for the world's largest democracy, which is also one of the largest drugs and vaccine manufacturing countries. The article captures the bird's-eye-view of the problem of vaccine development, the policy of funding as well as procurement, and the politics of vaccine distribution in the country.

Cutaneous Complications of mRNA and AZD1222 COVID-19 Vaccines: A Worldwide Review.

Because of the increasing emergence of cutaneous reactions from COVID-19 vaccines worldwide, we investigated the published reports of these complications. We searched the PubMed, Google Scholar, and Scopus databases and the preprint server bioRxiv for articles on cutaneous complications linked to mRNA-1273 (Moderna), BNT162b2 (Pfizer–BioNTech), and AZD1222 (AstraZeneca–Oxford University) vaccines published until 30 September 2021. Eighty studies describing a total of 1415 reactions were included. Cutaneous reactions were more prevalent in females (81.6%). Delayed large local reactions were the most common complication (40.4%), followed by local injection site reactions (16.5%), zoster (9.5%), and urticarial eruptions (9.0%). Injection site and delayed large local reactions were predominantly caused by the mRNA-1273 vaccine (79.5% and 72.0%, respectively). BNT162b2 vaccination was more closely linked to distant reactions (50.1%) than mRNA-1273 (30.0%). Zoster was the most common distant reaction. Of reactions with adequate information for both vaccine doses, 58.3% occurred after the first dose only, 26.9% after the second dose only, and 14.8% after both doses. Overall, a large spectrum of cutaneous reaction patterns occurred following the COVID-19 vaccination. Most were mild and without long-term health implications. Therefore, the occurrence of such dermatologic complications does not contraindicate subsequent vaccination.

Omicron’s binding to sotrovimab, casirivimab, imdevimab, CR3022, and sera from previously infected or vaccinated individuals

SummarySARS-CoV-2 Omicron is the first pandemic variant of concern exhibiting an abrupt accumulation of mutations particularly in the receptor-binding domain that is a critical target of vaccination induced and therapeutic antibodies. Omicron's mutations did only marginally affect the binding of ACE2, and the two antibodies Sotrovimab and CR3022 but strongly impaired the binding of Casirivimab and Imdevimab. Moreover, as compared with Wuhan, there is reduced serum reactivity and a pronounced loss of competitive surrogate virus neutralization (sVN) against Omicron in naïve vaccinees and in COVID-19 convalescents after infection and subsequent vaccination. Finally, although the booster vaccination response conferred higher titers and better sVN, the effect was nonetheless significantly lower compared with responses against Wuhan. Overall, our data suggest that the antigenicity of Omicrons receptor binding motive has largely changed but antibodies such as Sotrovimab targeting other conserved sites maintain binding and therefore hold potential in prophylaxis and treatment of Omicron-induced COVID-19.

Longitudinal Aspects of VITT

In hundreds of patients worldwide, vaccination against COVID-19 with adenovirus vector vaccines (ChAdOx1 nCoV-19; Ad26.COV2.S) triggered platelet-activating anti-platelet factor 4 (PF4) antibodies inducing vaccine-induced immune thrombotic thrombocytopenia (VITT). In most VITT patients, platelet-activating anti-PF4-antibodies are transient and the disorder is discrete and non-recurring. However, in some patients platelet-activating antibodies persist, associated with recurrent thrombocytopenia and sometimes with relapse of thrombosis despite therapeutic-dose anticoagulation. Anti-PF4 IgG antibodies measured by enzyme-immunoassay (EIA) are usually detectable for longer than platelet-activating antibodies in functional assays, but duration of detectability is highly assay-dependent. As more than 1 vaccination dose against COVID-19 is required to achieve sufficient protection, at least 69 VITT patients have undergone subsequent vaccination with an mRNA vaccine, with no relevant subsequent increase in anti-PF4 antibody titers, thrombocytopenia, or thrombotic complications. Also, re-exposure to adenoviral vector-based vaccines in 5 VITT patients was not associated with adverse reactions. Although data are limited, vaccination against influenza also appears to be safe. SARS-CoV-2 infection reported in 1 patient with preceding VITT did not influence anti-PF4 antibody levels. We discuss how these temporal characteristics of VITT provide insights into pathogenesis.

BCG-induced trained immunity enhances acellular pertussis vaccination responses in an explorative randomized clinical trial

Acellular pertussis (aP) booster vaccines are central to pertussis immunization programs, although their effectiveness varies. The Bacille Calmette-Guérin (BCG) vaccine is a prototype inducer of trained immunity, which enhances immune responses to subsequent infections or vaccinations. While previous clinical studies have demonstrated that trained immunity can protect against heterologous infections, its effect on aP vaccines in humans is unknown. We conducted a clinical study in order to determine the immunological effects of trained immunity on pertussis vaccination. Healthy female volunteers were randomly assigned to either receive BCG followed by a booster dose of tetanus-diphteria-pertussis inactivated polio vaccine (Tdap-IPV) 3 months later (BCG-trained), BCG + Tdap-IPV concurrently, or Tdap-IPV followed by BCG 3 months later. Primary outcomes were pertussis-specific humoral, T- and B-cell responses and were quantified at baseline of Tdap-IPV vaccination and 2 weeks thereafter. As a secondary outcome in the BCG-trained cohort, ex vivo leukocyte responses were measured in response to unrelated stimuli before and after BCG vaccination. BCG vaccination 3 months prior to, but not concurrent with, Tdap-IPV improves pertussis-specific Th1-cell and humoral responses, and also increases total memory B cell responses. These responses were correlated with enhanced IL-6 and IL-1β production at the baseline of Tdap-IPV vaccination in the BCG-trained cohort. Our study demonstrates that prior BCG vaccination potentiates immune responses to pertussis vaccines and that biomarkers of trained immunity are the most reliable correlates of those responses.

Effectiveness of the BNT162b2 Vaccine after Recovery from Covid-19

BackgroundThe risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decreases substantially among patients who have recovered from coronavirus disease 2019 (Covid-19). However, it is unknown how long protective immunity lasts. Current guidelines recommend vaccination of recovered patients even though data regarding vaccine effectiveness in such cases are still limited.MethodsIn this retrospective cohort study, we reviewed electronic medical records from a large health care organization in Israel to assess reinfection rates in patients who had recovered from SARS-CoV-2 infection before any vaccination against Covid-19. We compared reinfection rates among patients who had subsequently received the BNT162b2 vaccine (Pfizer–BioNTech) and those who had not been vaccinated between March 1 and November 26, 2021. We used a Cox proportional-hazards regression model with time-dependent covariates to estimate the association between vaccination and reinfection after adjustment for demographic factors and coexisting illnesses. Vaccine effectiveness was estimated as 1 minus the hazard ratio. In a secondary analysis, we evaluated the vaccine effectiveness of one dose as compared with two doses.ResultsA total of 149,032 patients who had recovered from SARS-CoV-2 infection met the eligibility criteria. Of these patients, 83,356 (56%) received subsequent vaccination during the 270-day study period. Reinfection occurred in 354 of the vaccinated patients (2.46 cases per 100,000 persons per day) and in 2168 of 65,676 unvaccinated patients (10.21 cases per 100,000 persons per day). Vaccine effectiveness was estimated at 82% (95% confidence interval [CI], 80 to 84) among patients who were 16 to 64 years of age and 60% (95% CI, 36 to 76) among those 65 years of age or older. No significant difference in vaccine effectiveness was found for one dose as compared with two doses.ConclusionsAmong patients who had recovered from Covid-19, the receipt of at least one dose of the BNT162b2 vaccine was associated with a significantly lower risk of recurrent infection.

The Incidence of SARS-CoV-2 Reinfection in Persons With Naturally Acquired Immunity With and Without Subsequent Receipt of a Single Dose of BNT162b2 Vaccine : A Retrospective Cohort Study.

There is insufficient evidence regarding the magnitude and durability of protection conferred by a combined effect of naturally acquired immunity after SARS-CoV-2 infection and vaccine-induced immunity. To compare the incidence rate of SARS-CoV-2 reinfection in previously infected persons to that of previously infected persons who subsequently received a single dose of BNT162b2 messenger RNA vaccine. A retrospective cohort study emulating a randomized controlled target trial through a series of nested trials. Nationally centralized database of Maccabi Healthcare Services, Israel. Persons with documented SARS-CoV-2 infection who did not receive subsequent SARS-CoV-2 vaccination were compared with persons with documented SARS-CoV-2 infection who received a single dose of the BNT162b2 vaccine at least 3 months after infection. Forty-one randomized controlled trials were emulated, in which 107413 Maccabi Healthcare Services' members aged 16 years and older were eligible for at least 1 trial. SARS-CoV-2-related outcomes of infection, symptomatic disease, hospitalization, and death, between 2 March and 13 December 2021. A statistically significant decreased risk (hazard ratio, 0.18 [95% CI, 0.15 to 0.20]) for reinfection was found among persons who were previously infected and then vaccinated versus those who were previously infected but remained unvaccinated. In addition, there was a decreased risk for symptomatic disease (hazard ratio, 0.24 [CI, 0.20 to 0.29]) among previously infected and vaccinated persons compared with those who were not vaccinated after infection. No COVID-19-related mortality cases were found. Hybrid protection against non-Delta variants could not be inferred. Persons previously infected with SARS-CoV-2 gained additional protection against reinfection and COVID-19 from a subsequent single dose of the BNT162b2 vaccine. Nonetheless, even without a subsequent vaccination, reinfection appeared relatively rare. None.

A naturally hypersensitive porcine model may help understand the mechanism of COVID-19 mRNA vaccine-induced rare (pseudo) allergic reactions: complement activation as a possible contributing factor

A tiny fraction of people immunized with lipid nanoparticle (LNP)-enclosed mRNA (LNP-mRNA) vaccines develop allergic symptoms following their first or subsequent vaccinations, including anaphylaxis. These reactions resemble complement (C) activation-related pseudoallergy (CARPA) to i.v. administered liposomes, for which pigs provide a naturally oversensitive model. Using this model, we injected i.v. the human vaccination dose (HVD) of BNT162b2 (Comirnaty, CMT) or its 2-fold (2x) or 5-fold (5x) amounts and measured the hemodynamic changes and other parameters of CARPA. We observed in 6 of 14 pigs transient pulmonary hypertension along with thromboxane A2 release into the blood and other hemodynamic and blood cell changes, including hypertension, granulocytosis, lymphopenia, and thrombocytopenia. One pig injected with 5x CMT developed an anaphylactic shock requiring resuscitation, while a repeat dose failed to induce the reaction, implying tachyphylaxis. These typical CARPA symptoms could not be linked to animal age, sex, prior immune stimulation with zymosan, immunization of animals with Comirnaty i.v., or i.m. 2 weeks before the vaccine challenge, and anti-PEG IgM levels in Comirnaty-immunized pigs. Nevertheless, IgM binding to the whole vaccine, used as antigen in an ELISA, was significantly higher in reactive animals compared to non-reactive ones. Incubation of Comirnaty with pig serum in vitro showed significant elevations of C3a anaphylatoxin and sC5b-9, the C-terminal complex. These data raise the possibility that C activation plays a causal or contributing role in the rare HSRs to Comirnaty and other vaccines with similar side effects. Further studies are needed to uncover the factors controlling these vaccine reactions in pigs and to understand their translational value to humans.

Pityriasis rosea–like rash after messenger RNA COVID-19 vaccination: A case report and review of the literature

A spectrum of cutaneous reactions to SARs-CoV-2 (COVID-19) vaccines have been reported in the literature. We present a case of a pityriasis rosea-like rash occurring after Pfizer COVID-19 vaccination and review cases of pityriasis rosea (PR)/PR-like eruption (PR-LE) after mRNA COVID-19 vaccine published in the medical literature. Of the 30 cases found, none experienced severe adverse effects and the rash resolved in an average of 5.6 weeks. It is important for physicians to be aware of this self-limited reaction so they can reassure and appropriately counsel patients that it is safe to receive subsequent vaccine doses despite the cutaneous eruption. Additionally, differences in incidence of this reaction after Pfizer and Moderna vaccination may suggest a differing host immune response incited by these vaccines which warrants further investigation.

Avoidable emergency department visits for rabies vaccination

BackgroundAdministering subsequent doses of rabies vaccine is not a medical emergency and does not require access to emergency department (ED) services. This study reviewed ED visits for rabies postexposure prophylaxis (PEP) to identify avoidable ED visits for subsequent rabies vaccination. MethodsThis retrospective study included patients who received human rabies immune globulin (HRIG) or rabies vaccine at 15 EDs of a multi-hospital health system from 2016 to 2018. All ED visits were classified as initial or non-initial healthcare visits after animal exposure. Emergency department visits for non-initial healthcare were classified as necessary (HRIG administration, worsening symptoms, other emergent conditions, or vaccination during a natural disaster) or avoidable (rabies vaccination only). ResultsThis study included 145 patients with 203 ED visits (113 initial and 90 non-initial healthcare visits). Avoidable ED visits were identified for 19% (28 of 145) of patients and 66% (59 of 90) of ED visits for non-initial healthcare. Contributing factors for avoidable ED visits were suboptimal ED discharge instructions to return to the ED for vaccination (n = 20 visits) and patients' inability to coordinate outpatient follow-up (n = 17 visits). Patients with previous avoidable ED visits had a 73% probability for unnecessarily returning to the ED for vaccination. The average number of avoidable ED visits observed per patient was 0.41 (95% CI = 0.25 to 0.56). Since the Centers for Disease Control and Prevention reports that 30,000 to 60,000 Americans initiates rabies PEP each year, we estimate that 7500 to 33,600 avoidable ED visits occur for rabies vaccination in the US each year. ConclusionsOne of 5 patients who received rabies PEP in the ED had avoidable ED visits for subsequent rabies vaccination. This study highlights systemic lack of coordination following ED discharge and barriers to accessing rabies vaccine.