Recent Vaccine Research Articles

European Society of Breast Imaging (EUSOBI) guidelines on the management of axillary lymphadenopathy after COVID-19 vaccination: 2023 revision

Axillary lymphadenopathy is a common side effect of COVID-19 vaccination, leading to increased imaging-detected asymptomatic and symptomatic unilateral axillary lymphadenopathy. This has threatened to negatively impact the workflow of breast imaging services, leading to the release of ten recommendations by the European Society of Breast Imaging (EUSOBI) in August 2021. Considering the rapidly changing scenario and data scarcity, these initial recommendations kept a highly conservative approach. As of 2023, according to newly acquired evidence, EUSOBI proposes the following updates, in order to reduce unnecessary examinations and avoid delaying necessary examinations. First, recommendation n. 3 has been revised to state that breast examinations should not be delayed or rescheduled because of COVID-19 vaccination, as evidence from the first pandemic waves highlights how delayed or missed screening tests have a negative effect on breast cancer morbidity and mortality, and that there is a near-zero risk of subsequent malignant findings in asymptomatic patients who have unilateral lymphadenopathy and no suspicious breast findings. Second, recommendation n. 7 has been revised to simplify follow-up strategies: in patients without breast cancer history and no imaging findings suspicious for cancer, symptomatic and asymptomatic imaging-detected unilateral lymphadenopathy on the same side of recent COVID-19 vaccination (within 12 weeks) should be classified as a benign finding (BI-RADS 2) and no further work-up should be pursued. All other recommendations issued by EUSOBI in 2021 remain valid.Graphical abstract

Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination

Background: People with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs) have attenuated IgG response following COVID-19 vaccination; however, the clinical consequences remain unclear. Objective: To report COVID-19 rates in pwMS according to vaccine serology. Methods: PwMS with available (1) serology 2–12 weeks following COVID-19 vaccine 2 and/or vaccine 3 and (2) clinical data on COVID-19 infection/hospitalisation were included. Logistic regression was performed to examine whether seroconversion following vaccination predicted risk of subsequent COVID-19 infection after adjusting for potential confounders. Rates of severe COVID-19 (requiring hospitalisation) were also calculated. Results: A total of 647 pwMS were included (mean age 48 years, 500 (77%) female, median Expanded Disability Status Scale (EDSS) 3.5% and 524 (81%) exposed to DMT at the time of vaccine 1). Overall, 472 out of 588 (73%) were seropositive after vaccines 1 and 2 and 222 out of 305 (73%) after vaccine 3. Seronegative status after vaccine 2 was associated with significantly higher odds of subsequent COVID-19 infection (odds ratio (OR): 2.35, 95% confidence interval (CI): 1.34–4.12, p = 0.0029), whereas seronegative status after vaccine 3 was not (OR: 1.05, 95% CI: 0.57–1.91). Five people (0.8%) experienced severe COVID-19, all of whom were seronegative after most recent vaccination. Conclusion: Attenuated humoral response to initial COVID-19 vaccination predicts increased risk of COVID-19 in pwMS, but overall low rates of severe COVID-19 were seen.

Coevolution based immunoinformatics approach considering variability of epitopes to combat different strains: A case study using spike protein of SARS-CoV-2

In the recent past several vaccines were developed to combat the COVID-19 disease. Unfortunately, the protective efficacy of the current vaccines has been reduced due to the high mutation rate in SARS-CoV-2. Here, we successfully implemented a coevolution based immunoinformatics approach to design an epitope-based peptide vaccine considering variability in spike protein of SARS-CoV-2. The spike glycoprotein was investigated for B- and T-cell epitope prediction. Identified T-cell epitopes were mapped on previously reported coevolving amino acids in the spike protein to introduce mutation. The non-mutated and mutated vaccine components were constructed by selecting epitopes showing overlapping with the predicted B-cell epitopes and highest antigenicity. Selected epitopes were linked with the help of a linker to construct a single vaccine component. Non-mutated and mutated vaccine component sequences were modelled and validated. The in-silico expression level of the vaccine constructs (non-mutated and mutated) in E. coli K12 shows promising results. The molecular docking analysis of vaccine components with toll-like receptor 5 (TLR5) demonstrated strong binding affinity. The time series calculations including root mean square deviation (RMSD), radius of gyration (RGYR), and energy of the system over 100 ns trajectory obtained from all atom molecular dynamics simulation showed stability of the system. The combined coevolutionary and immunoinformatics approach used in this study will certainly help to design an effective peptide vaccine that may work against different strains of SARS-CoV-2. Moreover, the strategy used in this study can be implemented on other pathogens.

Hospital Outcomes in Patients Hospitalized for COVID-19 Pneumonia: The Effect of SARS-CoV-2 Vaccination and Vitamin D Status.

SARS-CoV-2 vaccination promises to improve outcomes for patients with COVID-19 pneumonia (most notably those with advanced age and at high risk for severe disease). Here, we examine serum 25-Hydroxyvitamin D (25(OH)D) status and outcomes in both old (>70 years) and young vaccinated (n = 80) and unvaccinated (n = 91) subjects, who were hospitalized due to COVID-19 pneumonia in a single center (Connolly Hospital Dublin). Outcomes included ICU admission and mortality. Serum 25(OH)D levels were categorized as D30 (<30 nmol/L), D40 (30-49.99 nmol/L) and D50 (≥50 nmol/L). In multivariate analyses, D30 was independently associated with ICU admission (OR: 6.87 (95% CI: 1.13-41.85) (p = 0.036)) and mortality (OR: 24.81 (95% CI: 1.57-392.1) (p = 0.023)) in unvaccinated patients, even after adjustment for major confounders including age, sex, obesity and pre-existing diabetes mellitus. While mortality was consistently higher in all categories of patients over 70 years of age, the highest observed mortality rate of 50%, seen in patients over 70 years with a low vitamin D state (D30), appeared to be almost completely corrected by either vaccination, or having a higher vitamin D state, i.e., mortality was 14% for vaccinated patients over 70 years with D30 and 16% for unvaccinated patients over 70 years with a 25(OH)D level greater than 30 nmol/L. We observe that high mortality from COVID-19 pneumonia occurs in older patients, especially those who are unvaccinated or have a low vitamin D state. Recent vaccination or having a high vitamin D status are both associated with reduced mortality, although these effects do not fully mitigate the mortality risk associated with advanced age.

The seven-fold rise in incidence of Stevens-Johnson syndrome & toxic epidermal necrolysis: Associations with COVID-19 and the vaccine

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a rare, potentially life threatening mucocutaneous hypersensitivity reaction resulting in desquamation of the skin and mucosa. These patients are managed on burns units due to the widespread desquamation. We report the largest case series of participants developing SJS/TEN in the setting of recent COVID infection or vaccination. We found a seven-fold increase in SJS/TEN since the COVID pandemic. This increase correlates with an increase in COVID infections and vaccination rates. We explore the immunopathological relationships between COVID and SJS/TEN and propose theories for possible associations.

BI04 Cutaneous cryptococcosis: a post-transplant cat among the pigeons

Abstract Cryptococcosis is an infection caused by the encapsulated yeasts Cryptococcus neoformans and Cryptococcus gattii, which are opportunistic pathogens that mainly affect immunocompromised individuals. Infection is primarily by inhalation and causes pulmonary disease; haematogenous dissemination may affect other organs, particularly the central nervous system, with 10% of disseminated cryptococcosis affecting the skin. Primary cutaneous cryptococcosis due to direct skin inoculation is less common and rarely disseminates. We describe a kidney transplant recipient with disseminated cryptococcosis who presented with skin lesions in the early post-transplant period. As previously observed in a transplant patient with primary cutaneous cryptococcosis under our care, we propose that a history of close contact with urban pigeons was the source of infection. A 48-year-old man who had been transplanted in 2014 presented in May 2022 with a 3-cm-diameter, well-demarcated ulcer on his right shoulder which had been slowly enlarging over 6 weeks in close proximity to his recent COVID-19 vaccination site. Swab was positive for C. neoformans, serology was positive for cryptococcal antigen, chest X-ray showed a 14-mm nodule in the right lung and magnetic resonance imaging of the brain was normal. He was admitted by the transplant team and treated for presumed disseminated cryptococcal infection with intravenous AmBisome® and flucytosine for 2 weeks, and subsequently oral fluconazole. In view of his atypical presentation, we directly questioned him about previous skin disorders and possible sources of infection. It emerged that 6 months earlier, he had noticed multiple lesions on his legs but did not report this as they spontaneously resolved. Mobile phone images showed 0.5–1-cm umbilicated, red–purple nodules consistent with possible primary cutaneous cryptococcosis. We discovered that his balcony was covered in pigeons and their droppings, and he had unsuccessfully asked his local council to provide bird netting. This was the most likely source of his infection, although it is uncertain whether his skin involvement was primary, secondary or both, due to ongoing pigeon exposure. A 54-year-old female patient under our care who had previously presented 3 months post-transplant with extensive noduloulcerative umbilicated lesions confirmed on biopsy to be primary cutaneous cryptococcosis also had close contact with pigeons and their droppings in the immediate post-transplant period. The incidence of cryptococcosis in immunocompromised patients is increasing and cutaneous involvement may be the first manifestation of disseminated disease. The clinical spectrum of skin lesions is highly polymorphic, making diagnosis challenging. However, it should be considered in immunocompromised patients presenting with atypical skin lesions, particularly in the early post-transplant period.

The incidence of acute lower limb thrombosis, in symptomatic patients detected with ultrasound, with consideration of recent COVID‐19 vaccination or infection

AbstractIntroductionAfter the COVID‐19 vaccination roll out began in March 2021 patients began presenting to a Victorian Emergency Department with lower limb pain following their vaccination. As a result, radiology requests for ultrasound examinations, to exclude post vaccination deep vein thrombosis (DVT) began appearing.MethodA retrospective search of lower limb venous ultrasound examinations was undertaken for a 1‐year period from March 2021 to February 2022. Patients were included in the study if they had a clinical indication of having been referred following COVID‐19 vaccination. Bivariate analysis was conducted, using logistic regression, to determine the strength of association between independent variables (i.e., age, gender, vaccination status, and COVID‐19 diagnosis) and dependent variables (i.e., a diagnosis of DVT and superficial vein thrombosis [SVT]).ResultsThe study found 1627 examinations had a lower limb venous ultrasound examination over the study period. Ultrasound was positive for acute DVT in 218/1627 examinations (13.4%). 104/1627 (6.4%) presented for ultrasound following COVID‐19 vaccination. Six of these were found to have acute lower limb DVT detected. The association between post vaccination and DVT was an odds ratio (OR) of 0.379 (95% CI 0.164–0.874, p = .023). All examinations that were diagnosed with acute thrombus had recently received AstraZeneca (AZ) (Vaxzevria, ChAdOx1‐S/nCoV‐19) vaccine. Four examinations were diagnosed with superficial vein thrombosis (SVT) post recent COVID‐19 vaccination. One patient was diagnosed with Vaccine Induced Thrombosis with Thrombocytopenia after their first dose of AZ.ConclusionThis study found 6/1627 (0.37%) lower limb venous ultrasound examinations, over a 1‐year period, were positive for acute DVT after COVID‐19 vaccination. The results showed post vaccination examinations were less likely to be diagnosed with a DVT than the population referred who had not had recent vaccination.

Henoch-Schönlein purpura in a 6-year-old boy after initial COVID-19 vaccination

The COVID-19 pandemic has significantly impacted global health, and the widespread immunization of adults against SARS-CoV-2 has played a pivotal role in altering the course of the disease. While COVID-19 vaccine adverse events are generally uncommon and mild, the recent vaccination of the pediatric population has emphasized the need for vigilance and reporting of potential side effects. In this case report, we present a 6-year-old boy who developed Henoch-Schönlein purpura following the administration of the first dose of Pfizer-BioNTech BNT16B2b2 mRNA COVID-19 vaccine, making it the earliest reported case of such an adverse event. Our report highlights the importance of continued monitoring and reporting of adverse events in pediatric patients receiving the COVID-19 vaccine, as well as the need for prompt diagnosis and management of potential vaccine-related complications.

Omicron BA.1-containing mRNA-1273 boosters compared with the original COVID-19 vaccine in the UK: a randomised, observer-blind, active-controlled trial

The omicron BA.1 bivalent booster is used globally. Previous open-label studies of the omicron BA.1 (Moderna mRNA-1273.214) booster showed superior neutralising antibody responses against omicron BA.1 and other variants compared with the original mRNA-1273 booster. We aimed to compare the safety and immunogenicity of omicron BA.1 monovalent and bivalent boosters with the original mRNA-1273 vaccine in a large, randomised controlled trial. In this large, randomised, observer-blind, active-controlled, phase 3 trial in the UK (28 hospital and vaccination clinic sites), individuals aged 16 years or older who had previously received two injections of any authorised or approved COVID-19 vaccine, with or without an mRNA vaccine booster (third dose), were randomly allocated (1:1) using interactive response technology to receive 50 μg omicron BA.1 monovalent or bivalent vaccines or 50 μg mRNA-1273 administered as boosters via deltoid intramuscular injection. The primary outcomes were safety and immunogenicity at day 29, including prespecified non-inferiority and superiority of booster immune responses, based on the neutralising antibody geometric mean concentration (GMC) ratios of the monovalent and bivalent boosters compared with mRNA-1273. Safety was assessed in all participants who received first or second boosters, and primary immunogenicity outcomes were assessed in all participants who received the planned booster dose, had pre-booster and day 29 antibody data, had no major protocol deviations, and who were SARS-CoV-2-negative. The study is registered with EudraCT (2022-000063-51) and ClinicalTrials.gov (NCT05249829) and is ongoing. Between Feb 16 and March 24, 2022, 724 participants were randomly allocated to receive omicron BA.1 monovalent (n=366) or mRNA-1273 (n=357), and between April 2 and June 17, 2022, 2824 participants were randomly allocated to receive omicron BA.1 bivalent (n=1418) or mRNA-1273 (n=1395) vaccines as second boosters. Median durations (months) between the most recent COVID-19 vaccine and study boosters were similar for omicron BA.1 monovalent (4·0 months [IQR 3·6-4·7]) and mRNA-1273 (4·1 [3·5-4·7]), and for the omicron BA.1 bivalent (5·5 [4·8-6·2]) and mRNA-1273 (5·4 [4·8-6·2]) boosters. The omicron BA.1 monovalent and bivalent boosters elicited superior neutralising GMCs against the omicron BA.1 variant compared with mRNA-1273, with GMC ratios of 1·68 (99% CI 1·45-1·95) and 1·53 (1·41-1·67) at day 29 post-booster doses in participants without previous SARS-CoV-2 infection. Both boosters induced non-inferior ancestral SARS-CoV-2 (Asp614Gly) immune responses with GMCs that were similar for the bivalent (2987·2 [95% CI 2814·9-3169·9]) versus mRNA-1273 (2911·3 [2750·9-3081·0]) and lower for the monovalent (2699·7 [2431·3-2997·7] vs 3020·6 [2776·5-3286·2]) boosters, with respective GMC ratios of 1·05 (99% CI 0·96-1·15) and 0·82 (95% CI 0·74-0·91). Results were comparable regardless of previous SARS-CoV-2 infection status. Incidences of solicited adverse reactions with the omicron BA.1 monovalent (335 [91·3%] of 367 participants) and omicron BA.1 bivalent (1285 [90·4%] of 1421 participants) boosters were similar to those observed previously for mRNA-1273, with no new safety concerns identified and no occurrences of fatal adverse events. Omicron-containing booster vaccines generated superior immunogenicity against omicron BA.1 and comparable immunogenicity against the original strain with no new safety concerns. It remains important to continuously monitor the immune responses and real-world vaccine effectiveness as divergent SARS-CoV-2 variants emerge. Moderna.

Prothymosin-Alpha, a Novel and Sensitive Biomarker of the Inflammatory and Insulin-Resistant Statuses of Obese Individuals: A Pilot Study Involving Humans

Background: Obesity constitutes a chronic, low-grade inflammatory status that predisposes people to the development of insulin resistance and cardiometabolic complications. Hypoxia, a main pathological feature of visceral fat in obese individuals, has been shown to affect the secretome of murine 3T3-L1 adipose cells, causing the upregulation of prothymosin-alpha (ProT-α), which is a protein with immunomodulatory functions that was originally found in the thymus. The aim of this case–control observational study was to measure the circulating levels of ProT-α in obese and lean individuals and determine whether such levels are correlated with inflammatory and metabolic parameters. Methods: Sixty-one obese patients (BMI ≥ 30 Kg/m2) and fifty-one age-matched, lean controls (BMI 18.5–24.9 Kg/m2) were recruited in the Endocrinology Unit (“Mater-Domini”) of the University Hospital of Catanzaro, Italy. The exclusion criteria included affliction with acute and systemic inflammatory states (i.e., leukocytosis), recent infectious diseases or vaccinations, obesity complications (i.e., type 2 diabetes mellitus and cardiovascular diseases), hepatic or renal failure, pregnancy and lactation, cancer, use of drugs or alcohol, and smoking. Apart from routine biochemical determinations, serum samples were screened for the presence of ProT-α using an ELISA method and for the presence of a panel of inflammatory cytokines and growth factors via a multiparametric chemiluminescence micro-array. Results: Between the age-matched groups, no statistically significant differences were shown in relation to fasting glucose, HbA1c, liver function tests, lipid profiles, circulating interleukins (IL)-1α, -1β, -2, -4, -8, and -10, MCP-1, TNF-α, VEGF and EGF. Instead, significantly higher median levels were observed in obese patients vs. lean controls with respect to fasting insulin levels (p &lt; 0.001), a classic insulin resistance marker, and IL-6 (p = 0.004). In addition, ProT-α levels were significantly and considerably higher in obese patients compared to lean controls (median ProT-α, 600.0 vs. 411.5 pg/mL, p = 0.004) and showed a moderate to strong positive relationship with fasting insulin levels and selected cytokines (i.e., TNF-α and IL-8). Conclusions: An increase in circulating levels of ProT-α is linked with obesity and can be detected before any clinical cardiometabolic complications develop. ProT-α may represent a novel and sensitive biomarker for inflammation and insulin resistance in obese individuals.

#4600 MPO AND PR3 DUAL POSITIVE ANCA AND ANA: A CASE REPORT

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis has been thought to be a relatively rare disease, although it has been increasing in incidence recently likely due to improved testing and recognition. One of two main antigens are targeted in this condition, either proteinase 3 (PR3) or myeloperoxidase (MPO). Uncommonly, both antigens can be targeted in specific situations such as during levisamole use, propylthiouracil use, hydralazine use or infections. Herein, we illustrate a case of a patient who presented with progressively worsening kidney function in the setting of recent COVID booster. Method A 79 year old female with a history of hypertension, hyperlipidemia, acid reflux and hypothyroidism was admitted to our facility from her outpatient nephrologist due to abnormal labs. This was the first time the patient had seen a nephrologist, although she was told that her serum creatinine (SCr) was elevated to ∼3 mg/dL three months earlier. At that time, she noted blood tinged urine as well as frothiness of urine that had since resolved. She also endorsed a raised erythematous rash that also resolved. She did mention that she had increasing fatigue over the past week prior to presentation along with weight loss over the past few months. She denied ear pain, sinus pain, epistaxis, hemoptysis or specific joint pain. She denied any kidney stones or NSAID use. She was a former smoker, having quit decades ago. She denied any current tobacco or illicit drug use, including cocaine as well as any herbal supplements or medications that were not otherwise prescribed to her by a medical provider. She did note recent COVID booster prior to being told of a SCr ∼3 mg/dL. She had a repeat kidney function test one month prior to presentation, at which time she was told her SCr was 5 mg/dL. In our Emergency Department, SCr was elevated to 8.45 mg/dL with a BUN of 68 mg/dL. Computed tomography of the abdomen and pelvis ruled out any hydronephrosis or kidney stones. Urinalysis was revealing for 509 RBCs, 39 WBCs, WBC casts as well as granular casts. Spot urine protein to creatinine ratio was found to be elevated at 6925 mg/g. Serologies were pertinent for a positive ANA as well as ANCA. Interestingly, both MPO and PR3 titres were elevated at 72 AU/mL and 391 AU/mL, respectively. Kidney biopsy was performed and revealed a pauci-immune glomerulonephritis with crescents along with mixed interstitial inflammatory infiltrate (Figure 1). The diagnosis of dual positive ANCA glomerulonephritis was made. Computed tomography of the chest revealed scattered ground glass opacities and subpleural nodules which was consistent with a vasculitis. She started treatment with Rituximab and steroids on Day 5 of hospitalization. Results Although evidence linking ANCA vasculitis to COVID infection and vaccine has been starting to develop, the association with dual positive ANCA is something that has been elusive. Having titres for both MPO and PR3 ANCA is uncommon and has traditionally been attributed to very few causes; as COVID infection and vaccination has been a fairly recent development, this has not historically been considered a cause to think of in such patients. In the case presentation above, our patient had no other identifiable risk factors for presenting with a dual positive ANCA vasculitis. She did endorse recent booster vaccination which was subsequently followed by elevated SCr and positive serologies. Conclusion Dual positive ANCA vasculitis is an uncommon finding and should trigger a high clinical suspicion for implicated drugs, infections as well as COVID vaccination.

Assessment of Anti-SARS-CoV-2 antibody levels among university students vaccinated with different COVID-19 primary and booster doses — fall 2021, Wisconsin

BackgroundUniversity students commonly received COVID-19 vaccinations before returning to U.S. campuses in the Fall of 2021. Given likely immunologic variation among students based on differences in type of primary series and/or booster dose vaccine received, we conducted serologic investigations in September and December 2021 on a large university campus in Wisconsin to assess anti-SARS-CoV-2 antibody levels.MethodsWe collected blood samples, demographic information, and COVID-19 illness and vaccination history from a convenience sample of students. Sera were analyzed for both anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibody levels using World Health Organization standardized binding antibody units per milliliter (BAU/mL). Levels were compared across categorical primary COVID-19 vaccine series received and binary COVID-19 mRNA booster status. The association between anti-S levels and time since most recent vaccination dose was estimated by mixed-effects linear regression.ResultsIn total, 356 students participated, of whom 219 (61.5%) had received a primary vaccine series of Pfizer-BioNTech or Moderna mRNA vaccines and 85 (23.9%) had received vaccines from Sinovac or Sinopharm. Median anti-S levels were significantly higher for mRNA primary vaccine series recipients (2.90 and 2.86 log [BAU/mL], respectively), compared with those who received Sinopharm or Sinovac vaccines (1.63 and 1.95 log [BAU/mL], respectively). Sinopharm and Sinovac vaccine recipients were associated with a significantly faster anti-S decline over time, compared with mRNA vaccine recipients (P <.001). By December, 48/172 (27.9%) participants reported receiving an mRNA COVID-19 vaccine booster, which reduced the anti-S antibody discrepancies between primary series vaccine types.ConclusionsOur work supports the benefit of heterologous boosting against COVID-19. COVID-19 mRNA vaccine booster doses were associated with increases in anti-SARS-CoV-2 antibody levels; following an mRNA booster dose, students with both mRNA and non-mRNA primary series receipt were associated with comparable levels of anti-S IgG.

Correlating symptoms to infectivity among vaccinated healthcare workers with COVID-19

Background: Directing COVID-19 diagnostic testing to healthcare workers (HCWs) who are likely to be infected has potential to reduce staffing shortages and decrease opportunity for in-hospital transmission; however, HCWs with COVID-19 may exhibit a range of symptoms. We assessed the burden of symptoms in relation to cycle threshold (Ct) values as a surrogate for viral shedding in vaccinated healthcare workers. Methods: We retrospectively reviewed employee health records of COVID-19–vaccinated employees who tested positive for SARS-CoV-2 between December 2020 and January 2022 at 2 academic hospital systems. We reviewed demographic data, reasons for testing including symptoms, exposure history, medical history, vaccination dates, Ct values, and genotypes when available. We compared mean Ct values between symptomatic and minimally symptomatic cases using independent sample t tests. Patients were defined as minimally symptomatic if they had no symptoms or a single symptom that is not cough, fever, or anosmia at the time of testing. Patients were defined as more symptomatic if they reported &gt;1 symptom or cough, fever, or anosmia. Results: In total, 298 HCWs tested positive for COVID-19. Most positive cases were female (73%), white (78%), and had patient-facing roles (77%). Genotypic testing (n = 109) revealed that most genotypes belonged to the SARS-CoV-2 delta variant (AY lineages, B1.617.2). More cases were minimally symptomatic (62%) than were more symptomatic (38%). None required hospitalization during the study period. Mean Ct values (n = 141) showed no significant difference between more symptomatic and minimally symptomatic cases (19.8 vs 20.6; P = .40) (Fig. 1). Also, there was no significant difference in mean Ct value, comparing those with vaccination 90 days prior to positive (20.52 vs 19.88; P = .537). Conclusions: Our study shows no significant difference in cycle threshold values between minimally symptomatic and more symptomatic infections in vaccinated HCWs. In addition, HCWs exhibit high viral load even when infected within 90 days after vaccination. When considering whether to attend work, HCWs should be aware that mild symptoms and recent vaccination do not necessarily reflect low transmissibility and that they should follow CDC guidance regarding when to return to work.Disclosures: None

WED-152 - Hepatitis flare appeared to be more severe with poorer outcome in chronic hepatitis B patients with recent COVID vaccination during the COVID pandemic

WED-152 - Hepatitis flare appeared to be more severe with poorer outcome in chronic hepatitis B patients with recent COVID vaccination during the COVID pandemic

False positive PET scan in patients with treated malignancy following COVID-19 vaccination.

e18698 Background: The COVID-19 pandemic led to mass vaccination across the globe and resulted in several unintended consequences, one of which being reactive lymphadenopathy mimicking malignancy. A large study reported hypermetabolic lymphadenopathy (HLN) in over 45% of patients after receiving at least one dose of COVID-19 vaccine. A study on breast cancer patients noted a near-400% increase in lymphadenopathy on MRI and ultrasonography over the two years prior to mass vaccination. These findings present a dilemma in patients with treated malignancy while under surveillance. As vaccination became more commonplace, a case series reported on patients with PET-detected lymphadenopathy, with biopsies confirming VRLN. These investigations contributed to general recommendations on the importance of clinical context in patient care after COVID-19 vaccination. We present a unique study that evaluates patients with treated solid and hematological malignancies that presented with HLN after COVID-19 vaccination which emphasizes the importance of clinical acumen in the management of oncological patients in the pandemic era. Methods: We identified 6 patients aged 39-95 with prior malignancy. 5 were diagnosed with metastatic melanoma, and one had a diagnosis of high-grade B-cell lymphoma. Patients were managed with chemotherapy, immunotherapy, surgery, radiotherapy, or a combination of modalities, and were in complete radiological remission. All patients received at least two doses of a COVID-19 vaccine, with one dose at least three weeks prior to a routine surveillance PET-CT. Each patient exhibited HLN. Results: Of six patients, three underwent biopsy. There was no evidence of malignancy in any biopsy, and VRLN was confirmed. The remaining patients were followed with surveillance, and all had resolution of HLN without intervention. Time between COVID-19 vaccination and PET evidence of HLN ranged from 19 to 232 days. Time between first positive and first resolved PET ranged from 92 to 463 days. All patients were alive at the time of abstract submission. Conclusions: Our study emphasizes the importance of a focused history when suspecting recurrent malignancy, especially after sustained remission in our vulnerable populations. Acknowledging that COVID-19 vaccination can lead to HLN is becoming more common, and we show that this can occur, persist, and resolve even months after vaccination. While high suspicion for recurrence should be maintained, all efforts should be taken to protect patients and prevent unnecessary procedures. Records of recent vaccinations should be available and reviewed prior to radiological studies and clinical decisions, which can reduce avoidable interventions and harm. Surveillance of our patients proved to be an appropriate approach, and our study shows that similar patient presentations can have different paths of care depending on the awareness of treating physicians.

Influences of sociodemographic characteristics and parental HPV vaccination hesitancy on HPV vaccination coverage in five US states

BackgroundIn the United States (US), half of new human papillomavirus (HPV) infections occur among young people aged 15–24 years. Despite the effectiveness of HPV vaccination in protecting against HPV-associated cancers, its coverage among adolescents remains suboptimal. This study examined the association of sociodemographic characteristics and HPV vaccination hesitancy with HPV vaccination coverage in five US states with disproportionately low adolescent coverage rates compared to the national average. MethodsResponses to an online Qualtrics survey from 926 parents of children aged 9–17 years in Arkansas, Mississippi, Missouri, Tennessee, and Southern Illinois in July 2021 were analyzed using multivariate logistic regression to estimate the association of sociodemographic characteristics and HPV vaccination hesitancy with HPV vaccination coverage. ResultsOf the parents, 78 % were female, 76 % were non-Hispanic White, 61.9 % lived in rural areas, 22 % were classified as HPV vaccine hesitant, and 42 % had vaccinated their oldest child between the ages of 9–17 years against HPV. Children of vaccine hesitant parents were less likely to have received any doses of the HPV vaccine than children of non-vaccine hesitant parents (AOR: 0.17, 95 % CI:0.11–0.27). Male children were less likely to have initiated the HPV vaccine series than female children (AOR: 0.70, 95 % CI:0.50–0.97). Older children (13–17 vs 9–12 years), receiving the meningococcal conjugate or most recent seasonal influenza vaccine were all associated with higher likelihoods of receiving any doses of the HPV vaccine (AOR: 6.01, 95 % CI:3.98–9.08; AOR: 2.24, 95 % CI:1.27–3.95; AOR: 2.41, 95 % CI:1.73–3.36, respectively). ConclusionsAdolescent HPV vaccination coverage remains low in our targeted states. Children’s age, sex, and parental vaccine hesitancy were significantly associated with likelihood of HPV vaccination. These findings offer the opportunity for targeted interventions among parents in regions with low vaccine uptake and underscore the importance of developing and implementing strategies to address parental HPV vaccination hesitancy to improve uptake in the US.

Complement-dependent mpox-virus-neutralizing antibodies in infected and vaccinated individuals

Mpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. Following historic success of smallpox vaccination with vaccinia virus (VACV)-based vaccines, the third generation modified vaccinia Ankara (MVA)-based vaccine was used as prophylaxis for MPXV, but its effectiveness remains poorly characterized. Here, we applied two assays to quantify neutralizing antibodies (NAbs) in sera from control, MPXV-infected, or MVA-vaccinated individuals. Various levels of MVA NAbs were detected after infection, historic smallpox, or recent MVA vaccination. MPXV was minimally sensitive to neutralization. However, addition of complement enhanced detection of responsive individuals and NAb levels. Anti-MVA and -MPXV NAbs were observed in 94% and 82% of infected individuals, respectively, and 92% and 56% of MVA vaccinees, respectively. NAb titers were higher in individuals born before 1980, highlighting the impact of historic smallpox vaccination on humoral immunity. Altogether, our results indicate that MPXV neutralization is complement dependent and uncover mechanisms underlying vaccine effectiveness.

Recent Human Papillomavirus Vaccination is Associated with a Lower Risk of COVID-19: A US Database Cohort Study.

To explore the association between human papillomavirus (HPV)vaccination and risk of coronavirus disease 2019 (COVID-19). Specifically, our study aimed to test the hypothesis that HPV vaccination may also induce trained immunity, which would potentially reduce the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and improve clinical outcomes. Several vaccines have been reported to trigger non-specific immune reactions that could offer protection from heterologous infections. A recent case report showed that verruca vulgaris regressed after COVID-19, suggesting a possible negative association between COVID-19 and HPV infection. We enrolled 57,584 women with HPV vaccination and compared them with propensity score-matched controls who never received HPV vaccination in relation to the risk of COVID-19 incidence. Cox proportional hazard regression analysis was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses stratified by age, race, comorbid asthma, and obesity were performed. The risk of COVID-19 incidence was significantly lower in those who had recently received the HPV vaccine (within 1 year after HPV vaccination, aHR: 0.818, 95% CI 0.764-0.876; within 1-2 years after HPV vaccination, aHR: 0.890, 95% CI 0.824-0.961). Several limitations were recognized in this study, including residual confounding, problems of misclassification due to the use of electronic health record data, and that we were unable to keep track of the patients' HPV infection status and the HPV antibody levels in those who had received the vaccine. Recent HPV vaccination was associated with a lower risk of incident COVID-19 and hospitalization. Based on the promising protective effect of HPV vaccine shown in this study, these findings should be replicated in an independent dataset. Further studies are needed to provide a better understanding of the underlying mechanisms and the differences in risks among 2-, 4-, or 9-valent HPV vaccine recipients.

Severe rash after COVID-19 vaccination.

The patient's recent vaccine was the most remarkable thing about his medical history.

Evaluation of mortality risk after COVID-19 vaccination, Utah 2021.

In order to evaluate trends in death after COVID-19 vaccination we analyzed the timing of death relative to vaccination date and the causes of death in vaccinated Utahns in 2021. We matched people in the Utah immunization registry with documented COVID-19 vaccinations between December 18, 2020 and December 31, 2021 to Utah's 2021 vital statistics death records. Vaccinated people were categorized as having one, two, or≥three COVID-19 vaccine doses in a time-updated metric. We examined crude mortality rates by dosing groups in two-week intervals for all deaths, and by COVID-19 versus non-COVID-19 causes, within the 44weeks following receipt of the most recent vaccine. We identified 2,072,908 individuals who received at least one dose of COVID-19 vaccine of whom 10,997 died in 2021. Only 17.5% of the total vaccinated population was age 65+, while 80.9% of those who died were over 65. In the four weeks following the first or second vaccination, all-cause mortality was low and then stabilized for the remainder of the evaluation period at a bi-weekly average of 33.0 and 39.0 deaths/100,000 people for one and two doses, respectively. Typical seasonal variation in death was observed among those with two doses. Small sample size precluded analysis of those with≥three doses, but trends were similar. Mortality rates in the 44weeks following the COVID-19 vaccination did not show trends suggesting an increase in mortality related to COVID-19 vaccination, reinforcing the safety of COVID-19 vaccines. This represents an accessible approach for local evaluation.