A case of TAFRO syndrome after vaccination, successfully treated with cyclosporine.

BACKGROUND: TAFRO syndrome is a rare disorder that causes thrombocytopenia, generalized oedema, fever, organ enlargement, and renal impairment. Few reports have suggested an association with vaccines, and few cases have undergone renal biopsy. TAFRO syndrome is often severe and fatal, and its cause is unknown. We report a case of TAFRO syndrome that occurred after vaccination with the coronavirus disease 2019 (COVID-19) vaccine. CASE PRESENTATION: An 82-year-old woman received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Two weeks later, she was admitted to the hospital with oedema, accompanied with renal failure and thrombocytopenia. After close examination, she was diagnosed with TAFRO syndrome. She was treated with steroids, cyclosporine, and thrombopoietin receptor agonists. The patient was discharged after several months in remission. CONCLUSIONS: Although an incident of TAFRO syndrome after COVID-19 vaccination has been previously reported, this is a rare case in which the patient went into remission and was discharged. A renal biopsy was also performed in this case, which was consistent with previous reports. The favorable treatment course for TAFRO syndrome provides valuable insights.

An Unusual Presentation of Erythema Multiforme Following the Administration of Pfizer-BioNTech COVID-19 mRNA Vaccine in a Pediatric Patient.

Coronavirus disease 2019 (COVID-19) caused a global calamity that forced emergency use authorization to Pfizer-BioNTech COVID-19 (BNT162b2) vaccine. It is efficacious in preventing symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in seronegative recipients. The safety profile is still unclear; however, commonly reported symptoms post-vaccination are fatigue, headache, muscle pain, chills, and injection-site pain. COVID-19 disease elicits, to some extent, cutaneous side effects like urticaria, morbilliform rash, and chilblain-like eruption. Vaccination against COVID-19 was reported to induce similar dermatologic manifestations, such as urticarial rash, delayed large-local reaction, local injection-site reaction, and morbilliform eruption. Erythema multiforme (EM) is a rare manifestation post-vaccination, and only a few reports implicate it as a culprit in cutaneous eruptions following the BNT162b2 vaccine. This report delineates the presentation of a healthy 14-year-old girl to a dermatology clinic who developed EM post-vaccination with the first dose of BNT162b2. New-onset EM-eruption post-vaccination with BNT162b2 had been reported previously in 14 cases, and one case reported on the flare of preexisting-EM.

Avidity maturation of humoral response following primary and booster doses of BNT162b2 mRNA vaccine among nursing home residents and healthcare workers.

Infections, despite vaccination, can be clinically consequential for frail nursing home residents (NHR). Poor vaccine-induced antibody quality may add risk for such subsequent infections and more severe disease. We assessed antibody binding avidity, as a surrogate for antibody quality, among NHR and healthcare workers (HCW). We longitudinally sampled 112 NHR and 52 HCWs who received the BNT162b2 mRNA vaccine after each dose up to the Wuhan-BA.4/5-based Omicron bivalent boosters. We quantified anti-spike, anti-receptor binding domain (RBD), and avidity levels to the ancestral Wuhan, Delta, and Omicron BA.1 & 4/5 strains. The primary vaccination series produced substantial anti-spike and RBD levels which were low in avidity against all strains tested. Antibody avidity progressively increased in the 6-8 months that followed. Avidity significantly increased after the 1st booster but not for subsequent boosters. This study underscores the importance of booster vaccination among NHR and HCWs. The 1st booster dose increases avidity, increasing vaccine-induced functional antibody. The higher cross-reactivity of higher avidity antibodies to other SARS-CoV-2 strains should translate to better protection from ever-evolving strains. Higher avidities may help explain how the vaccine's protective effects persist despite waning antibody titers after each vaccine dose.

The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination.

BACKGROUND: Vaccine-related acute myocarditis is recognized as a rare and specific vaccine complication following mRNA-based COVID-19 vaccinations. The precise mechanisms remain unclear. We hypothesized that natural killer (NK) cells play a central role in its pathogenesis. METHODS: Samples from 60 adolescents with vaccine-related myocarditis were analyzed, including pro-inflammatory cytokines, cardiac troponin T, genotyping, and immunophenotyping of the corresponding activation subsets of NK cells, monocytes, and T cells. Results were compared with samples from 10 vaccinated individuals without myocarditis and 10 healthy controls. FINDINGS: Phenotypically, high levels of serum cytokines pivotal for NK cells, including interleukin-1ß (IL-1ß), interferon α2 (IFN-α2), IL-12, and IFN-γ, were observed in post-vaccination patients with myocarditis, who also had high percentage of CD57+ NK cells in blood, which in turn correlated positively with elevated levels of cardiac troponin T. Abundance of the CD57+ NK subset was particularly prominent in males and in those after the second dose of vaccination. Genotypically, killer cell immunoglobulin-like receptor (KIR) KIR2DL5B(-)/KIR2DS3(+)/KIR2DS5(-)/KIR2DS4del(+) was a risk haplotype, in addition to single-nucleotide polymorphisms related to the NK cell-specific expression quantitative trait loci DNAM-1 and FuT11, which also correlated with cardiac troponin T levels in post-vaccination patients with myocarditis. CONCLUSION: Collectively, these data suggest that NK cell activation by mRNA COVID-19 vaccine contributed to the pathogenesis of acute myocarditis in genetically and epidemiologically vulnerable subjects. FUNDING: This work was funded by the Hong Kong Collaborative Research Fund (CRF) 2020/21 and the CRF Coronavirus and Novel Infectious Diseases Research Exercises (reference no. C7149-20G).

Evaluating long-term antibody responses to booster doses of COVID-19 vaccines in the Pakistani population.

Background & Objective: Nearly 80 million of the Pakistani population received two doses of the BBIBP-CorV vaccine, against SARS-CoV-2, and 2.6 million people received heterologous booster doses up to February 2022. Our objective was to measure the long-term change of antibody titers in persons vaccinated with Pfizer-BioNTech COVID-19 following two doses of BBIBP-CorV. Methods: Serum specimens from forty-three participants were collected 4-8 weeks following two doses of BBIBP-CorV at the Indus Hospital & Health Network, Karachi. A second set of serum specimens were collected 2-12 months after Pfizer-BioNTech COVID-19 booster dose administration. Chemiluminescent Microparticle Immunoassay (CMIA, Abbott Alinity Quant), and the pseudotyped lentivirus antibody neutralization assay were performed on all specimens. The latter assay was reported as log half-maximal inhibitory concentrations (IC50), calculated using a nonlinear regression algorithm (log [inhibitor] versus normalized response variable slope) in Graph Pad Prism 9. Paired sample t-test was used to ascertain the statistical significance of the difference in means of antibody titers obtained before and after the booster vaccine doses. Results: Mean log10 values obtained with CMIA before and after the booster dose were 2.90 AU/mL and 3.87 AU/mL respectively, while the corresponding log10 IC50 values obtained through pseudotyped lentivirus antibody neutralization assay were 2.45 and 2.80. These differences were statistically significant with CMIA (p = <0.00001), but not with pseudotyped lentivirus antibody neutralization assay (p = 0.06318.). Conclusion: A heterologous booster dose with Pfizer-BioNTech COVID-19 vaccine following two doses of BBIBP results in increased total antibody titers, though neutralizing antibody titers may start to wane a few months after the booster dose.

Stronger and durable SARS-CoV-2 immune response to mRNA vaccines in 5-11 years old children with prior COVID-19.

BACKGROUND AND OBJECTIVES: mRNA vaccines elicit a durable humoral response to SARS-CoV-2 in adults, whereas evidence in children is scarce. This study aimed to assess the early and long-term immune response to the mRNA vaccine in children with or without previous SARS-CoV-2 infection. METHODS: In a multicentre prospective observational study, we profiled the immune response to the Pfizer BioNTech (BNT162b2) vaccine in 5-11-year-old children attending the University Pediatric Hospital of Padua and Bambino-Gesù Hospital in Rome (Italy) from December-2021 to February-2023. Blood samples were collected pre-, 1-, and 6-months after vaccination. Neutralizing antibodies (NAbs) and anti-spike-receptor-binding-domain (anti-S-RBD) IgG titers were analyzed through Plaque Reduction Neutralization Test (PRNT) and chemiluminescent immune-enzymatic assay (CLIA), respectively. Immune cell phenotypes were analyzed by flow cytometry. RESULTS: Sixty children (26 [43 %] female, median age = 8 years [IQR = 7-10.7]) were enrolled in the study, including 46 children with a laboratory-confirmed previous COVID-19 (SARS-CoV-2-recovered) and 14 SARS-CoV-2-naïve participants defined as the absence of antigen-specific antibodies before vaccination. SARS-CoV-2-recovered participants recorded higher anti-S-RBD IgG and Wild-type and Omicron BA.2 NAbs titers than SARS-CoV-2-naïve participants at both 1- and 6-months after vaccination. Antibody titers correlated with T (Tregs) and B (Bregs) regulatory cell frequencies in SARS-CoV-2-recovered children. Both SARS-CoV-2-recovered and SARS-CoV-2-naïve participants decreased antibody titers by approximately 100 to 250 % from 1 to 6 months. While children with immunocompromising underlying conditions developed immune responses comparable to those of healthy children, solid organ transplant recipients exhibited lower levels of NAbs and anti-S-RBD IgG titers, as well as reduced frequencies of Tregs and Bregs. CONCLUSIONS: mRNA vaccination triggered a higher production of specific anti-SARS-CoV-2 antibodies along with increased levels of regulatory cells in children with previous SARS-CoV-2 infection up to the following 6 months. These findings provide insights into boosting pre-existing immunity.

BNT162b2 Booster Dose Elicits a Robust Antibody Response in Subjects with Abdominal Obesity and Previous SARS-CoV-2 Infection.

Little is known about the long-term durability of the induced immune response in subjects with obesity, particularly in those with an abdominal distribution of adipose tissue. We evaluated SARS-CoV-2-specific antibody responses after BNT162b2 vaccine booster dose, comparing individuals with and without abdominal obesity (AO), discerning between individuals previously infected or not. IgG-TrimericS were measured in 511 subjects at baseline, on the 21st day after vaccine dose 1, and at 1, 3, 6, and 9 months from dose 2, and at 1 and 3 months following the booster dose. To detect SARS-CoV-2 infection, nucleocapsid antibodies were measured at baseline and at the end of the study. Multivariable linear regression evaluated the three-month difference in the absolute variation in IgG-TrimericS levels from booster dose, showing AO and SARS-CoV-2 infection status interactions (p = 0.016). Regardless of possible confounding factors and IgG-TrimericS levels at the booster dose, AO is associated with a higher absolute change in IgG-TrimericS in prior infected individuals (p = 0.0125). In the same regression model, no interaction is highlighted using BMI (p = 0.418). The robust response in the development of antibodies after booster dose, observed in people with AO and previous infection, may support the recommendations to administer a booster dose in this population group.

Dynamics of Serum-Neutralizing Antibody Responses in Vaccinees through Multiple Doses of the BNT162b2 Vaccine.

SARS-CoV-2 mRNA vaccines are administered as effective prophylactic measures for reducing virus transmission rates and disease severity. To enhance the durability of post-vaccination immunity and combat SARS-CoV-2 variants, boosters have been administered to two-dose vaccinees. However, long-term humoral responses following booster vaccination are not well characterized. A 16-member cohort of healthy SARS-CoV-2 naïve participants were enrolled in this study during a three-dose BNT162b2 vaccine series. Serum samples were collected from vaccinees over 420 days and screened for antigen (Ag)-specific antibody titers, IgG subclass distribution, and neutralizing antibody (nAb) responses. Vaccine boosting restored peak Ag-specific titers with sustained α-RBD IgG and IgA antibody responses when measured at six months post-boost. RBD- and spike-specific IgG4 antibody levels were markedly elevated in three-dose but not two-dose immune sera. Although strong neutralization responses were detected in two- and three-dose vaccine sera, these rapidly decayed to pre-immune levels by four and six months, respectively. While boosters enhanced serum IgG Ab reactivity and nAb responses against variant strains, all variants tested showed resistance to two- and three-dose immune sera. Our data reflect the poor durability of vaccine-induced nAb responses which are a strong predictor of protection from symptomatic SARS-CoV-2 infection. The induction of IgG4-switched humoral responses may permit extended viral persistence via the downregulation of Fc-mediated effector functions.

An analysis of reported cases of hemophagocytic lymphohistiocytosis (HLH) after COVID-19 vaccination.

Although COVID-19 vaccines are an effective public health tool to combat the global pandemic, serious adverse events, such as hemophagocytic lymphohistiocytosis (HLH), caused by them are a concern. In this systematic review, cases of HLH reported after COVID-19 vaccination have been examined to understand the relationship between the two and propose effective therapeutic strategies. Furthermore, ruxolitinib's potential as a cytokine inhibitor and its affinity for CD25 were initially assessed through molecular docking, aiming to aid targeted HLH therapy. PubMed and Web of Science databases were searched for published individual case reports on the occurrence of HLH after the administration of any COVID-19 vaccine. A total of 17 articles (25 patients) were included in this qualitative analysis. Furthermore, molecular docking was employed to investigate the therapeutic potential of ruxolitinib for HLH after COVID-19 vaccination. The mean age of patients who developed HLH after COVID-19 vaccination was 48.1 years. Most HLH episodes occurred after the BNT162b2 mRNA COVID-19 vaccination (14/25 cases) and to an extent after the ChAdOx1 nCov-19 vaccination (5/25 cases). Almost all affected patients received steroid and antibiotic therapy. Three patients died despite treatment because of esophagus rupture, neutropenic fever, bacteroides bacteremia, refractory shock, and encephalopathy and shock. Visual docking results of IL-2 Rα and ruxolitinib using the Discovery Studio 2019 Client software yielded a model score of 119.879. The findings highlight the importance of considering and identifying the adverse effects of vaccination and the possibility of using ruxolitinib for treating HLH after COVID-19 vaccination.

Humoral and Cellular Immune Response Elicited by the BNT162b2 COVID-19 Vaccine Booster in Elderly.

Although the safety and efficacy of COVID-19 vaccines in older people are critical to their success, little is known about their immunogenicity among elderly residents of long-term care facilities (LTCFs). A single-center prospective cohort study was conducted: a total IgG antibody titer, neutralizing antibodies against Wild-type, Delta Plus, and Omicron BA.2 variants and T cell response, were measured eight months after the second dose of BNT162b2 vaccine (T0) and at least 15 days after the booster (T1). Forty-nine LTCF residents, with a median age of 84.8 ± 10.6 years, were enrolled. Previous COVID-19 infection was documented in 42.9% of the subjects one year before T0. At T1, the IgG titers increased up to 10-fold. This ratio was lower in the subjects with previous COVID-19 infection. At T1, IgG levels were similar in both groups. The neutralizing activity against Omicron BA.2 was significantly lower (65%) than that measured against Wild-type and Delta Plus (90%). A significant increase of T cell-specific immune response was observed after the booster. Frailty, older age, sex, cognitive impairment, and comorbidities did not affect antibody titers or T cell response. In the elderly sample analyzed, the BNT162b2 mRNA COVID-19 vaccine produced immunogenicity regardless of frailty.

Hybrid Immunity Provides the Best COVID-19 Humoral Response in Immunocompromised Patients with or without SARS-CoV-2 Infection History.

Immunization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly limited the spread of coronavirus disease 2019 (COVID-19) and reduced the associated complications, especially mortality. To prolong immunity, an immune booster was implemented. We evaluated the role of SARS-CoV-2 infection history in the vaccination schedules of kidney and liver transplant recipients and patients with chronic kidney disease (CKD). To this end, we retrospectively analyzed the data of 78 solid organ transplantation (SOT) recipients and 40 patients with immunoglobulin A (IgA) nephropathy as representatives of the CKD group. Patients received two or three doses of the BNT162b2 vaccine. At the follow-up, antibody (Ab) titer, graft function, COVID-19 history, and patients' clinical condition were assessed. Ab level was higher after two doses in patients with a COVID-19 history over three doses in patients with no COVID-19 history. Compared to three doses, subjects who were administered two doses had a longer median time to infection. Positive antibodies, in response to the third dose, were not observed in up to 8.4% of SOT patients. The results show that the vaccination schedule should take into account the vaccine response rate and COVID-19 history. So-called hybrid immunity appears to be most efficient at providing humoral responses against SARS-CoV-2 infection in immunocompromised patients.

Homologous or heterologous COVID-19 vaccine schemes: comparison of immune responses and side effects.

Real-life data are needed regarding the appropriate time and selection of vaccination strategies, homologous or heterologous. We aimed to compare neutralizing antibody levels and side effects in different vaccination schemes. The study included 310 Health Care Workers (HCWs) vaccinated with 5 different schemes. Antispike/RBD IgG levels were measured between 28 and 60 days after the last dose. Side effects in participants were recorded, and pharmacovigilance records were reviewed from the outpatient vaccine clinic. Mean age of the participants was 38 ± 11 years of whom 226 (72.9%) were female, and 84 (27.1%) were male. After booster doses, increasing antibody levels were detected in all groups. Mean antibody levels were detected to be statistically lower in 3 doses of inactivated vaccines group. The side effects were no significant difference between groups. Booster dose administration with mRNA vaccines stands out as the most accurate strategy for those at risk of contracting severe COVID-19 and HCWs caring for this population.

Maternal Immunization During the Second Trimester with BNT162b2 mRNA Vaccine Induces a Robust IgA Response in Human Milk: A Prospective Cohort Study.

BACKGROUND: The human milk antibody response following maternal immunization with the BNT162b2 mRNA vaccine is important for the protection of the infant during infancy. The vaccine-specific antibody response is still unclear at different stages of human milk production, as are the effects of maternal immunization timing on the robustness of the antibody response. OBJECTIVES: The study aimed to assess the antibody response (IgG/IgA/IgM) during various lactation stages and identify the best vaccination timing during pregnancy. METHODS: A prospective cohort study of 73 postpartum women who were administered the BNT162b2 COVID-19 mRNA vaccine during the second or third trimester of pregnancy were recruited. Statistical comparison was conducted using 16 human milk samples from a prepandemic control group. RESULTS: Excluding 11 women, the study included 62 lactating women who were administered the mRNA vaccine during the second or third trimester of pregnancy. A total of 149 samples of human milk were collected at different lactation stages. Our findings reveal that colostrum exhibits significantly higher levels of IgG (95% confidence interval [CI]: 1.3, 9.0; P = 0.023), IgA (95% CI: 55.98, 100.2; P = 0.0034), and IgM (95% CI: 0.03, 0.62; P < 0.0001) compared with mature milk IgG (95% CI: 0.25, 0.43), IgA (95% CI: 9.65, 13.74), IgM (95% CI: 0.03, 0.04). The timing of maternal immunization affected the antibody response. The level of IgA in mature milk was higher when immunization occurred in the second trimester (95% CI: 11.14, 19.66; P = 0.006) than in the third trimester (95% CI: 7.16, 11.49). Conversely, IgG levels in mature milk were higher when immunization occurred during the third trimester (95% CI: 0.36, 0.65; P < 0.0001) than in the second trimester (95% CI: 0.09, 0.38). CONCLUSIONS: Our study provides evidence that administering the mRNA vaccine to pregnant women during the second trimester increases vaccine-specific IgA levels during lactation. Considering the significance of human milk IgA in mucosal tissues and its prevalence throughout lactation, it is reasonable to recommend maternal immunization with the BNT162b2 mRNA vaccine during the second trimester. This trial was registered at the Helsinki Committee of the Tel Aviv Medical Center as clinical trial number 0172-TLV.

The course of patients with hairy cell leukemia during the omicron surge of the Covid-19 pandemic.

In this study, we aim to explore the outcomes of Covid-19 infection in patients with Hairy cell leukemia (HCL). The cohort is based on data obtained from electronic medical records. It includes 218 consecutive patients diagnosed with HCL between 16 June 1998, and 20 September 2022, out of which the coronavirus has infected 85 patients during the Omicron surge. Out of 85 patients with HCL who were infected by Covid-19; 7 patients (8.2%) have been hospitalized, and the mortality rate was 2.3% (two patients). Thirteen of the 85 patients had been infected by Covid-19 in previous waves, including 9/13 after vaccination, and none of them developed a severe disease. Humoral immune response after three doses of the BNT162b2 mRNA vaccination regimen was evaluated in 40 patients and was attained in 67.5%. Based on multivariate analysis: unfavorable outcome was significantly more common in patients with HCL above 65 years old, who had at least one cytopenia, and with comorbidity of cardiovascular disease or asplenia. Our results indicates that the course of COVID-19 in patients with HCL during the Omicron wave has been improved relatively favorable.

COVID-19 mRNA vaccines as hypothetical epigenetic players: Results from an in silico analysis, considerations and perspectives.

OBJECTIVES: To investigate in silico the occurrence of epigenetic crosstalk by nucleotide sequence complementarity between the BNT162b2 mRNA vaccine and whole human genome, including coding and noncoding (nc)RNA genes. To correlate these results with those obtained with the original spike (S) gene of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2). METHODS: The publicly available FASTA sequence of the BNT162b2 mRNA vaccine and the SARS-CoV-2 isolate Wuhan-Hu-1 S gene (NC_045512.2) were used separately as key input to the Ensembl.org library to evaluate base pair match to human GRCh38 genome. Human coding and noncoding genes harboring hits were assessed for functional activity and health effects using bioinformatics tools and GWAS databases. RESULTS: The BLAT analysis against the human GRCh38 genome revealed a total of 37 hits for BNT162b2 mRNA and no hits for the SARS-CoV-2 S gene. More specifically, BNT162b2 mRNA matched 19 human genes whose protein products are variously involved in enzyme reactions, nucleotide or cation binding, signaling, and carrier functions. In BLASTN analysis of ncRNA genes, BNT162b2 mRNA and SARS-CoV-2 S gene matched 17 and 24 different human genomic regions, respectively. Overall, characterization of the matched noncoding sequences revealed stronger interference with epigenetic pathways for BNT162b2 mRNA compared with the original S gene. CONCLUSION: This pivotal in silico analysis shows that SARS-CoV-2 S gene and the BNT162b2 mRNA vaccine exhibit Watson-Crick nucleotide complementarity with human coding or noncoding genes. Although they do not share the same complementarity pattern, both may disrupt epigenetic mechanisms in target cells, potentially leading to long-term complications.

Intracranial Hemorrhage After Pfizer-BioNTech (BNT162b2) mRNA COVID-19 Vaccination: A Case Report.

The Coronavirus 2019 (COVID-19) pandemic has affected over 700 million people worldwide and caused nearly 7 million deaths. Vaccines currently developed or in development are the most effective tools for curbing the pandemic and mitigating its impacts. In Turkey, inoculation with the Pfizer-BioNTech COVID-19 vaccine (BNT162b2, also known as tozinameran) has been approved. We report a 56-year-old female patient with underlying essential hypertension who experienced intracranial hemorrhage after receiving her first dose of tozinameran. The patient underwent immediate surgical evacuation of the hematoma, during which a left middle cerebral artery bifurcation aneurysm was macroscopically identified and clipped. The patient was pronounced deceased on the second postoperative day. This is the second case of intracranial hemorrhage following tozinameran administration caused by a ruptured middle cerebral artery bifurcation aneurysm. Upon analyzing the case, there might be a connection between the vaccine's potential immune-triggering effect on hemodynamic patterns and the rupture of the previously unknown cerebral aneurysm. However, these severe complications do not justify avoiding vaccines; further studies are needed. This study emphasizes the need for increased vigilance in patients with underlying systemic comorbidities who have recently been vaccinated and to share our insights into the potential relationship between tozinameran and intracranial hemorrhage.

Guillain-Barré Syndrome Following the BNT162b2 mRNA COVID-19 Vaccine.

PURPOSE: The onset of the COVID-19 (SARS-CoV-2) pandemic in December 2019 created the need for multiple scientific research activities and clinical trials in an attempt to find solutions to mitigate the impact of the virus. One of the important tools to combat the virus is the development of vaccination programs. All types of vaccines have been associated with a mild to severe risk of neurological adverse events. One of these severe adverse events is Guillain-Barré syndrome. CASE REPORT: Here, we describe a case of Guillain-Barré syndrome after the first dose of the BNT162b2 mRNA COVID-19 vaccine and review the literature to increase the current knowledge regarding this complication. CONCLUSION: Guillain-Barré syndrome after COVID-19 vaccination is responsive to treatment. The benefits of administering the vaccine outweigh the risks. Due to the negative impact of COVID-19, it is essential to recognize the development of neurological complications that are potentially associated with vaccination, including Guillain-Barré syndrome.

Newly diagnosed extranodal NK/T-cell lymphoma, nasal type, at the injected left arm after BNT162b2 mRNA COVID-19 vaccination.

Anti-SARS-CoV-2 vaccines were developed in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the BNT162b2 mRNA vaccine is effective, adverse effects have been reported. Here, we report a case of extranodal NK/T-cell lymphoma, nasal type (ENKL), of the left arm following BNT162b2 mRNA vaccination. A 73-year-old male presented with a lump in the left arm, which was the site where he received the BNT162b2 mRNA vaccine 3 months prior. He was treated with topical corticosteroids and debridement, but the tumor progressed. Additionally, fever, night sweats, and general fatigue were observed. Laboratory findings included thrombocytopenia, elevated lactate dehydrogenase, and soluble interleukin-2 receptor levels. Skin biopsy led to a diagnosis of ENKL. The patient was treated with a 50% dose of SMILE therapy and radiotherapy, resulting in regression of the tumor. It seems that latent Epstein-Barr virus (EBV)-infected NK/T cells were reactivated by vaccination and contributed to the onset of ENKL. This is the first report of ENKL after BNT162b2 mRNA vaccination. The present case highlights the possible risk of development of malignant lymphoma, including ENKL at the injection site, after BNT162b2 COVID-19 vaccination.

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy.

Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with HIV infection on successful antiretroviral treatment and no previous SARS-CoV-2 infection. A total of 100 subjects (M/F 83/17, median age 54 years) were included in the analysis: 95 had plasma HIV RNA <40 copies/mL, the median CD4+ T cell count at the administration of the third dose was 580 cells/mm3, and the median nadir CD4+ T cell count was 258 cells/mm3. Neutralizing antibodies (NtAb) against B.1 were detectable in all the subjects, but those to BA.5 were only detected in 88 (p < 0.001). The median NtAb titer to B.1 was significantly higher than that to BA.5 (393 vs. 60, p < 0.0001), and there was a strong positive correlation between the paired measurements (p < 0.0001). Linear regression on a subset of 87 patients excluding outlier NtAb titers showed that 48% of the changes in NtAb titers to BA.5 are related to the changes in value titers to B.1. SARS-CoV-2 variants evolve rapidly, challenging the efficacy of vaccines, and data on comparative NtAb responses may help in tailoring intervals between vaccine doses and in predicting vaccine efficacy.

Kinetics and ability of binding antibody and surrogate virus neutralization tests to predict neutralizing antibodies against the SARS-CoV-2 Omicron variant following BNT162b2 booster administration.

OBJECTIVES: To assess the long-term humoral immunity induced by booster administration, as well as the ability of binding antibody and surrogate virus neutralization tests (sVNT) to predict neutralizing antibodies (NAbs) against the SARS-CoV-2 Omicron variant. METHODS: A total of 269 sera samples were analyzed from 64 healthcare workers who had received a homologous booster dose of BNT162b2. Neutralizing antibodies assessed by sVNT and anti-RBD IgG measured with the sCOVG assay (Siemens Healthineers®) were analyzed at five timepoints; before and up to 6 months following the booster. Antibody titers were correlated with neutralizing antibodies against the Omicron BA.1 variant obtained by pseudovirus neutralization test (pVNT) as a reference method. RESULTS: While Wild-type sVNT percentage of inhibition (POI) remained above 98.6% throughout the follow-up period after booster administration, anti-RBD IgG and NAbs assessed by Omicron BA.1 pVNT showed respectively a 3.4-fold and 13.3-fold decrease after 6 months compared to the peak reached at day 14. NAbs assessed by Omicron sVNT followed a steady decline until reaching a POI of 53.4%. Anti-RBD IgG and Omicron sVNT assays were strongly correlated (r=0.90) and performed similarly to predict the presence of neutralizing antibodies with Omicron pVNT (area under the ROC: 0.82 for both assays). In addition, new adapted cut-off values of anti-RBD IgG (>1,276 BAU/mL) and Omicron sVNT (POI>46.6%) were found to be better predictors of neutralizing activity. CONCLUSIONS: This study showed a significant drop in humoral immunity 6 months after booster administration. Anti-RBD IgG and Omicron sVNT assays were highly correlated and could predict neutralizing activity with moderate performance.