Four cases of audio-vestibular disorders related to immunisation with SARS-CoV-2 mRNA vaccines.

OBJECTIVE: To gain medical insight into the clinical course and safety of otolaryngologic disorders following immunisation with severe acute respiratory coronavirus (SARS-CoV-2) mRNA-based vaccines. DESIGN: Case description. STUDY SAMPLE: We report four cases of transient audio-vestibular symptoms, which occurred shortly after inoculation of two BNT162b2 (Pfizer-BioNTech®) and mRNA-1273 (Moderna®) vaccines. RESULTS: Hearing loss was unilateral in all cases and recovered at least partially: it was associated with persistent gait instability in two cases, after 1 and 7 months. Trigger mechanisms underpinning audio-vestibular impairment remain uncertain. Immune tolerance mechanisms with off-target innate activation of T-lymphocytes may be involved in vestibulocochlear nerve disorders, as for other cranial nerves involvement. CONCLUSIONS: The occurrence of audio-vestibular manifestations following mRNA-based vaccines needs ENT monitoring to support their causality in such rare vaccine-related adverse events. Audio-vestibular disorders appeared of transitory nature, including hearing loss, and should not deter further efforts in large-scale vaccination campaigns against SARS-CoV-2.

COVID-19 mRNA Vaccines: The Molecular Basis of Some Adverse Events.

Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. Unfortunately, the degree of inflammation produced by COVID-19 mRNA vaccines is variable, probably depending on genetic background and previous immune experiences, which through epigenetic modifications could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V).

Adverse cardiac events following mRNA COVID-19 vaccination: A systematic review and meta-analysis

Context: Although have been proven able to control the prevalence of coronavirus disease-19 (COVID-19), Pfizer-BioNTech and Moderna COVID-19 vaccines are reported to have possible side effects on the heart. Aims: To know the magnitude of adverse events in the cardiac after messenger ribonucleic acid (mRNA)-based vaccination. Methods: An electronic search in PubMed, Web of Science, Scopus, and Ebsco/Cinahl was performed. The keywords were: "COVID-19 vaccine”, "SARS-CoV-2 vaccine”, "myocarditis”, "myopericarditis”, "pericarditis”, "myocardial infarction”, and "myocardial injury”. The electronic search was updated until March 2022. STATA/MP Statistical Software: Release 14 (StataCorp LLC, College Station, Texas) was used in this study to perform a meta-analysis of a random-effect for myocarditis, pericarditis, myocarditis, myocardial infarction, and myocardial injury. Results: Twenty-one case reports/case series studies with a total of 62 individuals who had been vaccinated against COVID-19 mRNA (Pfizer-BioNTech and Moderna) were included in the systematic review. Whereas seven observational cohort studies had 170,053,333 people who had been vaccinated, 245 of whom had myocarditis. In addition, two observational cohort studies with 13,948,595 vaccinated individuals, 16 of whom developed pericarditis. There was only one observational cohort study that had a total of 7,183,889 people who had been vaccinated and 11 had myopericarditis. Based on the pooled incidence, the result is <0.002%. Conclusions: The Pfizer-BioNTech and Moderna vaccines have a low incidence of myocarditis. Men are more likely to develop post-COVID-19 myocarditis with an average age of 22 years and in the age range of 21-40 years. The type of mRNA COVID-19 vaccine that causes myocarditis the most is Pfizer. The diagnosis of myocarditis is mostly made by troponin examination. COVID-19 mRNA vaccination has a low incidence of myocarditis. © 2023 Journal of Pharmacy & Pharmacognosy Research.

Immunogenicity 6 months post COVID-19 mRNA-vaccination among adolescents with juvenile idiopathic arthritis on treatment with TNF-inhibitors.

OBJECTIVES: Mass vaccination is the most effective strategy for controlling the COVID-19 pandemic. This study aimed to evaluate the 6-month immunogenicity after BNT162b2-COVID-19 vaccination in adolescents with JIA on TNFi treatment. METHODS: This single-center study included adolescents with JIA treated with TNFi for at least 18 months. Patients received two doses of COVID-19 vaccine (Pfizer-BioNTech) from April 15th to May 15th 2021. Quantitative measurement of IgG antibodies to SARS-CoV-2-spike-protein-1 was performed at 1,3 and 6 months post-vaccination. RESULTS: Overall, 21 adolescents with JIA in clinical remission at the time of vaccinations were enrolled. None of them discontinued TNFi/MTX treatment at the time of vaccine administration or during the follow-up period. All patients developed a sustained humoral response against SARS-CoV-2 at 1 and 3 months after vaccination (p< 0.05). The antibody levels decreased significantly at 6 months post-vaccination (p< 0.01). The type of JIA did not reveal any differences in the humoral response at 3 (p= 0.894) or 6 months post-vaccination (p= 0.72). No difference was detected upon comparison of the immunogenicity between the different treatment arms (adalimumab vs etanercept) at 3 (p= 0.387) and 6 months (p= 0.526), or TNFi monotherapy vs combined therapy (TNFi plus methotrexate) at 3 (p= 0.623) and 6 months (p= 0.885). CONCLUSIONS: Although mRNA vaccines develop satisfactory immunogenicity at 1- and 3-months post-vaccination in adolescents with JIA on TNFi, SARS-CoV-2 antibody titers decrease significantly overtime, remaining at lower levels at 6 months. Further collaborative studies are required to determine long-term immunogenicity, real duration of immune protection and the need for a booster vaccine dose.

A Rare Case of MDA-5-Positive Amyopathic Dermatomyositis with Rapidly Progressive Interstitial Lung Disease Following COVID-19 mRNA Vaccination - a Case Report.

We report a rare case of new-onset MDA-5-positive amyopathic dermatomyositis with rapidly progressive interstitial lung disease (RP-ILD) following the second dose of the COVID-19 mRNA vaccine. Our patient was a previously healthy Asian female in her 60 s who presented with fatigue, dyspnea on exertion, and typical dermatomyositis (DM) rashes without muscle involvement two weeks after receiving the second dose of the COVID-19 mRNA BNT162b2 vaccine. Workup revealed high titer MDA-5 antibodies, abnormal pulmonary function tests, and ground-glass opacities on chest imaging. She had good response to early aggressive therapy with high-dose steroids, intravenous (IV) rituximab, mycophenolate mofetil, and intravenous immunoglobulin (IVIG). This case highlights the potential immunogenicity of COVID-19 mRNA vaccines and the possibility of new-onset systemic rheumatic syndromes after vaccination. More studies are needed to understand a definitive causal relationship and improve surveillance of adverse immunological events following COVID-19 vaccinations.

Translation suppression underlies the restrained COVID-19 mRNA vaccine response in the high-risk immunocompromised group.

Background: Immunocompromised (IC) patients show diminished immune response to COVID-19 mRNA vaccines (Co-mV). To date, there is no 'empirical' evidence to link the perturbation of translation, a rate-limiting step for mRNA vaccine efficiency (VE), to the dampened response of Co-mV. Materials and methods: Impact of immunosuppressants (ISs), tacrolimus (T), mycophenolate (M), rapamycin/sirolimus (S), and their combinations on Pfizer Co-mV translation were determined by the Spike (Sp) protein expression following Co-mV transfection in HEK293 cells. In vivo impact of ISs on SARS-CoV-2 spike specific antigen (SpAg) and associated antibody levels (IgGSp) in serum were assessed in Balb/c mice after two doses (2D) of the Pfizer vaccine. Spike Ag and IgGSp levels were assessed in 259 IC patients and 50 healthy controls (HC) who received 2D of Pfizer or Moderna Co-mV as well as in 67 immunosuppressed solid organ transplant (SOT) patients and 843 non-transplanted (NT) subjects following three doses (3D) of Co-mV. Higher Co-mV concentrations and transient drug holidays were evaluated. Results: We observed significantly lower IgGSP response in IC patients (p<0.0001) compared to their matched controls in 2D and 3D Co-mV groups. IC patients on M or S showed a profound dampening of IgGSP response relative to those that were not on these drugs. M and S, when used individually or in combination, significantly attenuated the Co-mV-induced Sp expression, whereas T did not exert significant influence. Sirolimus combo pretreatment in vivo significantly attenuated the Co-mV induced IgMSp and IgGSp production, which correlated with a decreasing trend in the early levels (after day 1) of Co-mV induced Sp immunogen levels. Neither higher Co-mV concentrations (6µg) nor withholding S for 1-day could overcome the inhibition of Sp protein levels. Interestingly, 3-days S holiday or using T alone rescued Sp levels in vitro. Conclusions: This is the first study to demonstrate that ISs, sirolimus and mycophenolate inhibited Co-mV-induced Sp protein synthesis via translation repression. Selective use of tacrolimus or drug holiday of sirolimus can be a potential means to rescue translation-dependent Sp protein production. These findings lay a strong foundation for guiding future studies aimed at improving Co-mV responses in high-risk IC patients.

Case report: Bilateral panuveitis resembling Vogt-Koyanagi-Harada disease after second dose of BNT162b2 mRNA COVID-19 vaccine.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a serious pandemic. COVID-19 vaccination is urgent needed for limiting SARS-CoV-2 outbreaks by herd immunity. Simultaneously, post-marketing surveillance to assess vaccine safety is important, and collection of vaccine-related adverse events has been in progress. Vision-threatening ophthalmic adverse events of COVID-19 vaccines are rare but are a matter of concern. We report a 45-year-old Japanese male with positive for HLA-DR4/HLA-DRB1*0405, who developed bilateral panuveitis resembling Vogt-Koyanagi-Harada (VKH) disease after the second dose of Pfizer-BioNTech COVID-19 mRNA (BNT162b2) vaccine. Glucocorticosteroid (GC) therapy combined with cyclosporine A (CsA) readily improved the panuveitis. The immune profile at the time of onset was analyzed using CyTOF technology, which revealed activations of innate immunity mainly consisting of natural killer cells, and acquired immunity predominantly composed of B cells and CD8+ T cells. On the other hand, the immune profile in the remission phase was altered by GC therapy with CsA to a profile composed primarily of CD4+ cells, which was considerably similar to that of the healthy control before the vaccination. Our results indicate that BNT162b2 vaccine may trigger an accidental immune cross-reactivity to melanocyte epitopes in the choroid, resulting in the onset of panuveitis resembling VKH disease.

Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency.

Immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines in primary antibody deficiencies (PADs) are largely unknown. We investigated antibody and CD4+ T-cell responses specific for SARS-CoV-2 spike protein (S) before and after vaccination and associations between vaccine response and patients' clinical and immunological characteristics in PADs. The PAD cohort consisted of common variable immune deficiency (CVID) and other PADs, not meeting the criteria for CVID diagnosis (oPADs). Anti-S IgG, IgA, and IgG subclasses 1 and 3 increased after vaccination and correlated with neutralization activity in HCs and patients with oPADs. However, 42% of CVID patients developed such responses after the 2nd dose. A similar pattern was also observed with S-specific CD4+ T-cells as determined by OX40 and 4-1BB expression. Patients with poor anti-S IgG response had significantly lower levels of baseline IgG, IgA, CD19+ B-cells, switched memory B-cells, naïve CD8+ T-cells, and a higher frequency of EM CD8+ T-cells and autoimmunity compared to patients with adequate anti-S IgG responses. Patients with oPADs can develop humoral and cellular immune responses to vaccines similar to HCs. However, a subset of CVID patients exhibit impairment in developing such responses, which can be predicted by the baseline immune profile and history of autoimmunity.

Immunogenicity of COVID-19 mRNA vaccines in hemodialysis patients: Systematic review and meta-analysis.

Background and Aims: Vaccine response is a concern in hemodialysis patients. Given that hemodialysis patients were not included in clinical trials, we aimed to synthesize the available evidence on the immunogenicity of coronavirus disease 2019 (COVID-19) mRNA vaccines in hemodialysis patients. Methods: We searched Scopus, PubMed, Sciencedirect, and finally google scholar databases for studies on COVID-19 mRNA-vaccines immunogenicity in hemodialysis patients up to December 1, 2021. Eligible articles measured antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike or Receptor-Binding Domain Antibody (S/RBD) postimmunization with COVID-19 mRNA vaccines. The immunogenicity of the vaccine was evaluated using seroconversion rates measured between 21 and 30 days after the first immunization and between 14 and 36 days post the second dose. We included studies including participants without a history of COVID-19 before vaccination. Healthy controls or health-care workers served as the control groups. After selecting eligible articles, the data were finally extracted from included articles. We used a random effects model to estimate the pooled seroconversion rate after COVID-19 mRNA vaccine administration. We assessed the heterogeneity between studies with the I 2 statistical index. Result: We selected 39 eligible citations comprising 806 cases and 336 controls for the first dose and 6314 cases and 927 controls for the second dose for statistical analysis. After the first dose of mRNA vaccines, the seroconversion rate was 36% (95% confidence interval [CI]: 0.24-0.47) and 68% (95% CI: 0.45-0.91) in hemodialysis patients and the control group, respectively. While seroconversion rate after the second dose of mRNA vaccines was 86% (95% CI: 0.81-0.91) and 100% (95% CI: 1.00-1.00) in hemodialysis patients and the control group, respectively. Conclusion: Although the immune response of hemodialysis patients to the second dose of the SARS-CoV-2 mRNA vaccine is very promising, the seroconversion rate of dialysis patients is lower than healthy controls. Periodically assessment of antibody levels of hemodialysis patients at short intervals is recommended.

Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products.

Polyethylene glycol (PEG) is a versatile polymer that is widely used as an additive in foods and cosmetics, and as a carrier in PEGylated therapeutics. Even though PEG is thought to be less immunogenic, or perhaps even non-immunogenic, with a variety of physicochemical properties, there is mounting evidence that PEG causes immunogenic responses when conjugated with other materials such as proteins and nanocarriers. Under these conditions, PEG with other materials can result in the production of anti-PEG antibodies after administration. The antibodies that are induced seem to have a deleterious impact on the therapeutic efficacy of subsequently administered PEGylated formulations. In addition, hypersensitivity to PEGylated formulations could be a significant barrier to the utility of PEGylated products. Several reports have linked the presence of anti-PEG antibodies to incidences of complement activation-related pseudoallergy (CARPA) following the administration of PEGylated formulations. The use of COVID-19 mRNA vaccines, which are composed mainly of PEGylated lipid nanoparticles (LNPs), has recently gained wide acceptance, although many cases of post-vaccination hypersensitivity have been documented. Therefore, our review focuses not only on the importance of PEGs and its great role in improving the therapeutic efficacy of various medications, but also on the hypersensitivity reactions attributed to the use of PEGylated products that include PEG-based mRNA COVID-19 vaccines.

Venous Thromboembolism following Two Doses of COVID-19 mRNA Vaccines in the US Population, 2020-2022.

The COVID-19 mRNA vaccine is one of the most effective strategies used to fight against COVID-19. Recently, venous thromboembolism (VTE) events after COVID-19 mRNA vaccination have been reported in various research. Such a concern may hamper the ongoing COVID-19 vaccination campaign. Based on the US Vaccine Adverse Event Reporting System data, this modified self-controlled case series study investigated the association of COVID-19 mRNA vaccination with VTE events among US adults. We found the VTE incidence rate in the recommended dose interval does not change significantly after receiving COVID-19 mRNA vaccines. This conclusion still holds if the analysis is stratified by age and gender. The VTE onset may not be significantly associated with COVID-19 mRNA vaccination.

Protective antibody response to mRNA-1273 and BNT162b2 vaccines in patients on maintenance haemodialysis: a prospective cohort study.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is more frequent and severe in patients with chronic kidney disease (CKD) on maintenance haemodialysis (HD). Vaccines are now available, but the protective response rates and determinants of humoral response to the vaccine are poorly described. Methods: This prospective observational study describes the response rates of detectable and protective antibody titres 1 month after each dose of an mRNA vaccine in a cohort of 851 patients on maintenance HD. Findings: Among naïve SARS-CoV-2 patients, a vast majority produced detectable (95.2%) or protective levels of antibodies (69.6%) 1 month after the second vaccine dose. In addition, the response rate was significantly higher with the mRNA-1273 than with the BNT162b2 vaccine 1 month after the second dose (79.8 versus 59.1%, respectively; P < 0.001). The main determinants for an inadequate humoral response were older age, treatment with immunosuppressants or oral anticoagulants and low serum albumin. All the patients who encountered coronavirus disease 2019 before vaccination also reached a highly protective humoral response. Interpretation: We found an acceptable humoral response rate in patients on maintenance HD, much higher than in transplant recipients. Therefore the third dose of vaccine may be justified in those patients with an inadequate humoral response, particularly those with a history of organ transplantation or immunosuppressive treatment.

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

BACKGROUND: The 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. METHODS: Fourteen 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. RESULTS: Serum 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. CONCLUSIONS: The 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.

mRNA Vaccines as an Efficient Approach for the Rapid and Robust Induction of Host Immunity Against SARS-CoV-2.

Among the currently used COVID-19 vaccines, the mRNA-based vaccines drew the interest of the scientists because of its potent and versatile nature in mitigating the disease efficiently through increased translation as well as the robust modulation of the innate and adaptive immune responses within the host. The naked or lipid encapsulated mRNAs are usually optimized in order to formulate the vaccine. One of the interesting advantage of using mRNA vaccines is that such platform can even be used to mitigate other infectious diseases like influenza, zika, and rabies. However, the leading COVID-19 mRNA vaccines, i.e., mRNA-1273 and BNT162b2, have already been noticed to possess around 95% efficacy in provoking both the humoral and cell mediated immunity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, causing the ongoing COVID-19 pandemic.

Population-Based Incidence, Severity, and Risk Factors Associated with Treated Acute-Onset COVID-19 mRNA Vaccination-Associated Hypersensitivity Reactions.

BACKGROUND: COVID-19 mRNA vaccination-associated acute-onset hypersensitivity reactions have caused anxiety and may be contributing to vaccine hesitancy. OBJECTIVE: To determine the incidence, severity, and risk factors for treated acute-onset COVID-19 mRNA vaccination-associated hypersensitivity reactions in a well-characterized population. METHODS: All Kaiser Permanente Southern California (KPSC) members who received COVID-19 mRNA vaccinations between December 15, 2020, and March 11, 2021, at a KPSC facility were identified and characterized, along with all treated acute-onset vaccination-associated hypersensitivity events. RESULTS: We identified 391,123 unique vaccine recipients (59.18% female, age 64.19 ± 17.86 years); 215,156 received 2 doses (53.54% Moderna), 157,615 only a first dose (50.13% Moderna) (1961 [1.46%] >2 weeks late getting a second dose), and 18,352 (74.43% Moderna) only a second dose. Only 104 (0.028%) (85.58% female, age 53.18 ± 15.96 years) had treated first dose events, 68 (0.030%) Moderna. Only 32 (0.014%) (93.75% female, age 57.28 ± 17.09 years) had treated second dose events, 21 (0.016%) Moderna. Only 2 (0.00033%) vaccinations resulted in anaphylaxis. Only 27 (20.77%) of those with treated first dose reactions failed to get a second dose. Only 6 of 77 (7.8%) with first dose reactions also had second dose reactions. Individuals with treated events were more likely to be female (P < .0001), younger (P < .0001), and had more pre-existing drug "allergies" (2.11 ± 2.12 vs 1.02 ± 1.41 [P < .0001] for average recipients). CONCLUSIONS: Treated acute-onset hypersensitivity events were mostly benign, more common with first COVID-19 mRNA vaccine doses, more likely to occur in younger females with typical risk factors associated with multiple drug intolerance syndrome, and very unlikely to be primarily immunologically mediated.

Review of Ribosome Interactions with SARS-CoV-2 and COVID-19 mRNA Vaccine.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causing pathogen of the unprecedented global Coronavirus Disease 19 (COVID-19) pandemic. Upon infection, the virus manipulates host cellular machinery and ribosomes to synthesize its own proteins for successful replication and to facilitate further infection. SARS-CoV-2 executes a multi-faceted hijacking of the host mRNA translation and cellular protein synthesis. Viral nonstructural proteins (NSPs) interact with a range of different ribosomal states and interfere with mRNA translation. Concurrent mutations on NSPs and spike proteins contribute to the epidemiological success of variants of concern (VOCs). The interactions between ribosomes and SARS-CoV-2 represent attractive targets for the development of antiviral therapeutics and vaccines. Recently approved COVID-19 mRNA vaccines also utilize the cellular machinery, to produce antigens and trigger immune responses. The design features of the mRNA vaccines are critical to efficient mRNA translation in ribosomes, and are directly related to the vaccine's efficacy, safety, and immunogenicity. This review describes recent knowledge of how the SARS-CoV-2 virus' genomic characteristics interfere with ribosomal function and mRNA translation. In addition, we discuss the current learning of the design features of mRNA vaccines and their impacts on translational activity in ribosomes. The understanding of ribosomal interactions with the virus and mRNA vaccines offers the foundation for antiviral therapeutic discovery and continuous mRNA vaccine optimization to lower the dose, to increase durability and/or to reduce adverse effects.

Evidence for retained spike-binding and neutralizing activity against emerging SARS-CoV-2 variants in serum of COVID-19 mRNA vaccine recipients.

BACKGROUND: Highly efficacious vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed. However, the emergence of viral variants that are more infectious than the earlier SARS-CoV-2 strains is concerning. Several of these viral variants have the potential to partially escape neutralizing antibody responses, warranting continued immune-monitoring. METHODS: We used a panel of 30 post-mRNA vaccination sera to determine neutralization and RBD and spike binding activity against a number of emerging viral variants. The virus neutralization was determined using authentic SARS-CoV-2 clinical isolates in an assay format that mimics physiological conditions. FINDINGS: We tested seven currently circulating viral variants of concern/interest, including the three Iota sublineages, Alpha (E484K), Beta, Delta and Lambda in neutralization assays. We found only small decreases in neutralization against Iota and Delta. The reduction was stronger against a sub-variant of Lambda, followed by Beta and Alpha (E484K). Lambda is currently circulating in parts of Latin America and was detected in Germany, the US and Israel. Of note, reduction in a receptor binding domain and spike binding assay that also included Gamma, Kappa and A.23.1 was negligible. INTERPRETATION: Taken together, these findings suggest that mRNA SARS-CoV-2 vaccines may remain effective against these viral variants of concern/interest and that spike binding antibody tests likely retain specificity in the face of evolving SARS-CoV-2 diversity. FUNDING: This work is part of the PARIS/SPARTA studies funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. In addition, this work was also partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384), by anonymous donors and by the Serological Sciences Network (SeroNet) in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024, Task Order No. 75N91020F00003.

Lichenoid cutaneous skin eruption and associated systemic inflammatory response following Pfizer-BioNTech mRNA COVID-19 vaccine administration.

The global effects of coronavirus disease 2019 (COVID-19) have driven unprecedented rapid development and mass deployment of vaccinations against the novel coronavirus. However, the short- and long-term adverse reactions following COVID-19 vaccinations are still under investigation as insufficient time has passed to fully explore these. The Pfizer-BioNTech COVID-19 mRNA vaccine has thus far shown a favourable safety profile in phase I-III studies. Although infrequent cases of generalized cutaneous reactions and systemic inflammatory response have been reported following other mRNA vaccines, these have not been reported following the Pfizer-BioNTech vaccine. We report a case of generalized lichenoid skin eruptions and systemic inflammatory response occurring together following the first dose of the Pfizer-BioNTech vaccine. Our case report adds to an accumulating body of literature connecting autoimmunity with the pathophysiology of the novel coronavirus disease.