A case of possible drug-induced liver injury due to COVID-19 vaccine.

The patient presented with nausea, appetite loss, and fatigue. She had received two doses of Pfizer/BioN-Tech BNT162b2 mRNA vaccine (COMIRNATY) for coronavirus disease 2019 (COVID-19). Acute liver injury was noted 14 days after the first dose of the vaccine. Re-exposure through the second dose worsened the liver injury. After liver biopsy on the third day of admission, methylprednisolone (1000 mg) was administered. Liver histology showed acute hepatitis with diffuse lobular inflammation/necrosis and lymphocyte-dominant infiltra-tion in the portal areas. The patient was diagnosed with drug-induced liver injury due to the COVID-19 vaccine based on the Digestive Disease Week Japan 2004 (DDW-J) scale, which assesses the temporal relationship, liver biopsy, and laboratory findings. With improvements in the blood test parameters, prednisolone was gradually tapered and stopped. One month later, no biochemical signs of relapse were noted. To our knowledge, this is the first report describing liver injury after the administration of the Pfizer COVID-19 vaccine in Japan.Copyright © 2022 The Japan Society of Hepatology.

Clinical features, diagnosis, and management of COVID-19 vaccine-associated Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada (VKH) disease is a rare and serious ocular adverse reaction following COVID-19 vaccination. This study aimed to evaluate the clinical features, diagnosis and management of COVID-19 vaccine-associated VKH disease. Case reports of VKH disease after COVID-19 vaccination were collected up to February 11, 2023 for retrospective analysis. Twenty-one patients (9 males and 12 females) were included, with a median age of 45 years (range 19-78), from three main regions, Asia (12/21), the Mediterranean region (4/21), and South America (5/21). Fourteen patients developed symptoms after the first dose of the vaccine, and 8 after the second dose. Vaccines included mRNA vaccine (10 cases), virus vector vaccine (6 cases), and inactivated vaccine (5 cases). The average time interval from vaccination to onset of symptoms was 7.5 days (range 12 hours to 4 weeks). All 21 patients experienced visual impairment after vaccination, with 20 cases involving both eyes. Sixteen patients showed symptoms of meningitis. Serous retinal detachment was observed in 16 patients, choroidal thickening was observed in 14, aqueous cell in 9, and subretinal fluid in 6. CSF pleocytosis was detected in 7 patients and skin symptoms were found in 3 patients. All patients received corticosteroid therapy, and 8 also received immunosuppressive agents. All patients recovered well, with a mean recovery time of 2 months. Early diagnosis and early treatment are crucial to the prognosis of patients with VKH after vaccination with COVID-19 vaccine. The risk of vaccination against COVID-19 in patients with a history of VKH disease should be evaluated clinically.

Novel risk patterns of vasovagal reactions in NZ blood donations complicated by COVID-19 restrictions.

Introduction: Vasovagal reactions (VVRs) are common but complex donor adverse reactions (DAEs) in blood donations. VVRs have been extensively studied with a multitude of risk factors identified including young age, female gender and first-time donor status. How they may interplay remains obscure. Methods: A total of 1,984,116 blood donations and 27,952 immediate VVRs (iVVRs) and 1,365 delayed VVRs (dVVRs) reported between 2011 and 2021 in NZ were used in multivariate logistic regression analyses each concerning donations with iVVRs as cases and those free of DAEs as controls. For each analysis stepwise selection was used to identify the best model and risk factors carrying significant main effects and/or interactions. Identified interactions informed further in-depth regression analyses to dissect iVVR risk patterns. Results: Over 95% of VVRs were iVVRs that had lower female preponderance and deferrals than dVVRs. iVVRs had a school seasonal pattern in whole blood donations driven by first-time donors from schools/colleges, and interactions between gender and age group differentiating the first-time from repeat donations. Subsequent regression analyses identified the known and novel risk factors of year and mobile collection sites and their interactions. iVVR rates were roundly elevated in 2020 and 2021 probably because of COVID-19 restrictions like facemask wearing. Exclusion of the 2020 and 2021 data removed the interactions with year, but confirmed interactions of gender with mobile collection sites (p = 6.2e-07) in first-time donations only and with age group in repeat donations only (p < 2.2e-16), together indicating young female donors at the highest risk of iVVRs. Our results also revealed that donation policy changes contributed to the year effects; donors had a lower iVVR risk at mobile sites than well-medicalized donation centers probably because of under-reporting. Conclusion: Modeling statistical interactions is valuable in identifying odds and revealing novel iVVR risk patterns and insights into blood donations.

A case of acute generalized exanthematous pustulosis following COVID-19 infection and remdesivir.

We report a challenging AGEP case following COVID-19 infection and a history of remdesivir use. Our study highlights the importance of considering history of COVID-19 and remdesivir as possible causative factors when visiting new-onset AGEP patients.

A case of persistent, confluent maculopapular erythema following a COVID-19 mRNA vaccination is possibly associated with the intralesional spike protein expressed by vascular endothelial cells and eccrine glands in the deep dermis.

Here, we report an 86-year-old Japanese woman presenting with confluent maculopapular erythema, which developed following the second dose of COVID-19 Messenger RNA (mRNA) vaccine (BNT162b2). Her skin lesions spread over time and persisted for more than 3 months. Surprisingly, immunohistochemical staining of the lesion 100 days after the disease onset revealed the COVID-19 spike protein expressed by vascular endothelial cells and eccrine glands in the deep dermis. As she had no episode of COVID-19 infection, it is highly likely that the spike protein was derived from the mRNA vaccine and it might be the cause of the development and persistence of her skin lesions. Her symptoms were prolonged and intractable until oral prednisolone was given.

Analysis of adverse reactions of lopinavir/ritonavir in the treatment of coronavirus disease 2019.

Objective: To explore the occurrence of adverse reactions of lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19). Method(s): The medical records of patients with COVID-19 who received LPV/r treatment in the Fourth People's Hospital of Nanning from January 24th to February 6th, 2020 were collected and the occurrence of adverse events during the treatment was retrospectively analyzed. According to the 5 principles of adverse drug reaction correlation evaluation proposed in the Handbook of Adverse Drug Reaction Reporting and Monitoring in China, adverse events that were certainly related, probably related, and possibly related to LPV/r were defined as LPV/r-related adverse reactions. The incidence of adverse reactions was calculated and the main clinical manifestations and severity of adverse reactions [grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death);grade 3-5 was defined as severe adverse reaction] were analyzed. Result(s): A total of 28 patients were enrolled in the analysis, including 13 males and 15 females, aged from 18 to 70 years with an average age of 44 years. The courses of treatment with LPV/r of patients ranged from 2 to 12 days, with a median course of 6 days. Of the 28 patients, 18 developed LPV/r related adverse reactions, with an incidence of 64.3%. The LPV/r-related adverse reactions in 18 patients included gastrointestinal reactions in 14 patients (grade 1 in 13 patients and grade 2 in 1 patient), bradycardia in 2 patients (grade 2 in both patients), and acute hemolysis in 1 patient (grade 3), and liver injury in 1 patient (grade 3), and no grade 4 or 5 adverse reactions occurred. The incidence of severe adverse reactions was 7.1%. Thirteen patients with grade 1 adverse reactions did not affect the treatment, and the symptoms were relieved after 2-7 days of continuous medication. LPV/r was discontinued in 5 patients with grade 2 or 3 adverse reactions, 4 of whom received symptomatic treatment, and the symptoms disappeared 2-10 days later. Conclusion(s): The incidence of adverse reactions in COVID-19 patients treated with LPV/r in our hospital was 64.3%. LPV/r mainly leads to mild gastrointestinal reactions and can also lead to bradycardia, acute hemolysis, and liver injury. Blood routine, liver function, and electrocardiogram need to be monitored during the treatment.Copyright © 2020 by the Chinese Medical Association.

Rapidly progressing generalized bullous fixed drug eruption after the first dose of COVID-19 messenger RNA vaccination.

Generalized bullous fixed drug eruption (GBFDE) is a rare type of life-threatening severe cutaneous adverse reaction that is considered a medical emergency because of its potential lethality. Currently, only a few cases of bullous adverse reactions have been reported after coronavirus disease 2019 (COVID-19) vaccination. We describe a patient with distinct clinical, histopathological, and immunological findings that are consistent with severe GBFDE, after Pfizer messenger RNA COVID-19 vaccination. An 83-year-old man presented with a fever and well-demarcated multiple erythematous patches that occurred only 4 h after receiving the first dose of COVID-19 Pfizer vaccination. Over the next few days, the patches became generalized and turned into blisters covering approximately 30% of the body surface. The patient was started on intravenous methylprednisolone and oral cyclosporine. There were no additional blistering lesions after 10 days of treatment, prompting a gradual dose reduction. Our case suggests that a stepwise vaccination adhering to the standard dosing schedule should be warranted with close monitoring for possible significant side effects.

6th European Pharmacovigilance Congress

The proceedings contain 25 papers. The topics discussed include: methodologies for evaluating drugs' benefit' risk balance as per current guidelines;CIOMS Working Group XII on benefit'risk of medicines;what are severe cutaneous adverse reactions (SCARs)? A dermatologic perspective;is artificial intelligence in pharmacovigilance on a 'hype cycle'?;artificial intelligence in pharmacovigilance;characterizing the safety profile of hematopoietic stem cell (HSC) gene therapies;long-term safety issues associated with genetic therapies;efficient road to reliable pharmacovigilance regulatory intelligence;post-marketing data collection and evidence evaluation;Uppsala monitoring center and WHO program of international drug monitoring;and safety monitoring of COVID-19 therapy and vaccines.

Experts' consensus on severe acute respiratory syndrome coronavirus-2 vaccination of children.

At present, severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is still rampant worldwide.As of September 10, 2021, there were about 222 million confirmed cases of corona virus disease 2019(COVID-19)and more than 4.6 million deaths worldwide.With the development of COVID-19 vaccines and the gradual vaccination worldwide, the increasing number of cases in children and unvaccinated young people has drawn attention.According to World Health Organization surveillance data, the proportion of COVID-19 infection cases in children gradually increased, and the proportion of cases in the age groups of under 5 years and 5-14 years increased from 1.0% and 2.5% in January 2020 to 2.0% and 8.7% in July 2021, respectively.At present, billions of adults have been vaccinated with various COVID-19 vaccines worldwide, and their protective effects including reducing infection and transmission, reducing severe disease and hospitalization, and reducing death, as well as high safety have been confirmed.Canada, the United States, Europe and other countries have approved the emergency COVID-19 vaccination in children and adolescents aged 12 to 17 years, and China has also approved the phased vaccination of COVID-19 vaccination in children and adolescents aged 3 to 17 years. For smooth advancement and implementation of COVID-19 vaccination in children, academic institutions, including National Clinical Research Center for Respiratory Diseases, National Center for Children's Health, and The Society of Pediatrics, Chinese Medical Association organized relevant experts to reach this consensus on COVID-19 vaccination in children.Copyright © 2021 by the Chinese Medical Association.

Adverse Effects Following the First and Second Dose in Individuals Receiving the Pfizer/BioNTech COVID-19 Vaccine: A Cohort Study

The FDA-approved vaccine against the novel coronavirus developed by Pfizer and BioNTech became widely popular in Iraq. The study aims to evaluate the incidence of vaccine adverse reactions, and severity after first and second doses and to link some of the demographic criteria of recipients. This study included 850 adults (16 years and older), and the sample was collected from a randomly selected vaccination center in Baghdad, Iraq for the period January to March 2022. Study Participants were directly interviewed while taking the first dose. Later on, phone calls were used to monitor participants' self-reported local or systemic adverse reactions for one week after the first dose and second dose. The participants' age range was (19-76 years) with a mean of (46.2 ± 15.8) years. 59.9% were males. The mean body mass index (BMI) was (27.7 ±2.9). The incidence of vaccine adverse reactions after first and second doses were: first dose (local 17%, systemic 27%), second dose (local 27%, systemic 35%). Ordinal logistic regression analysis after adjusting for age, sex, and past medical history (PMHx) showed a higher incidence and severity in females and those with PMHx in nearly all the types of reactions except for chills (second dose) and PMHx (two doses), muscle or joint pain (two doses). Spearman's Rank test showed an insignificant correlation with any type of reaction. The vaccine is generally safe and adverse reactions are mild and tolerable in the majority of cases. ©2022 by authors, all rights reserved.

Challenges and Recent Advancements in COVID-19 Vaccines.

Vaccination is the most effective method for the prevention of COVID-19 caused by SARS-CoV-2, which is still a global epidemic. However, the evolution of SARS-CoV-2 is so rapid that various variants, including the Alpha, Beta, Gamma, Delta, and Omicron variants, have emerged, lowering the protection rate of vaccines and even resulting in breakthrough infections. Additionally, some rare but severe adverse reactions induced by COVID-19 vaccines may raise safety concerns and hinder vaccine promotion; however, clinical studies have shown that the benefits of vaccination outweigh the risks caused by adverse reactions. Current vaccines approved with emergency use authorization (EUA) were originally adaptive for adults only, and infants, children, and adolescents are not included. New-generation vaccines are needed to overcome the challenges of limited adaptive age population, breakthrough infection (mainly due to virus variant emergencies), and critical adverse reactions. Fortunately, some advances in COVID-19 vaccines have been obtained regarding enlarged adaptive populations for clinical applications, such as the Pfizer/BioNTech vaccine and the Moderna vaccine. In this article, we provide a review on the challenges and recent advancements in COVID-19 vaccines. The development of next-generation COVID-19 vaccines should lay emphasis on the expansion of adaptive age populations in all individuals, the induction of immune responses to viral variants, the avoidance or alleviation of rare but potentially critical adverse reactions, and the discovery of subunit vaccines with adjuvants encapsulated in nanoparticles.

Furosemide-induced haemolytic anaemia in an extreme elderly patient.

Furosemide, a loop diuretic, is commonly used to treat fluid overload symptoms and heart failure. Drug-induced immune haemolytic anaemia is an unusual drug-adverse event. Furosemide-induced haemolysis is even rarer. This case report presents a 91-year-old male who developed acute haemolytic anaemia 3 days after initiating furosemide to treat myocardial infarction complicated with acute decompensated heart failure. He had increased lactate dehydrogenase and unconjugated bilirubin with undetectable haptoglobin, which indicated the destruction of red blood cells. Other causes for haemolytic anaemia, including hereditary, microangiopathic haemolytic anaemia, and paroxysmal nocturnal haemoglobinuria, were also excluded. He improved with drug cessation and a short course of glucocorticoids. This report aims to raise awareness of this rare complication caused by commonly prescribed drugs. Despite a negative result of a direct antiglobulin test, physicians must remain suspicious of drug-induced immune haemolytic anaemia in unclear cases of haemolysis.

CVSARRP: A framework to predict the risk of adverse to severe adverse reactions for 10855 diseases after COVID-19 vaccination.

COVID-19 vaccines greatly reduce the risk of infection with SARS-CoV-2. However, some people have adverse reactions after vaccination, and these can sometimes be severe. Gender, age, vaccines, and especially certain diseases histories are related to severe adverse reactions following COVID-19 vaccination. However, there are thousands of diseases and only some are known to be related to these severe adverse reactions. The risk of severe adverse reactions with other diseases remains unknown. Therefore, there is a need for predictive studies to provide improved medical care and minimize risk. Herein, we analyzed the statistical results of existing COVID-19 vaccine adverse reaction data and proposed a COVID-19 vaccine severe adverse reaction risk prediction method, named CVSARRP. The performance of the CVSARRP method was tested using the leave-one-out cross-validation approach. The correlation coefficient between the predicted and real risk is greater than 0.86. The CVSARRP method predicts the risk from adverse reactions to severe adverse reactions after COVID-19 vaccination for 10855 diseases. People with certain diseases, such as central nervous system diseases, heart diseases, urinary system disease, anemia, cancer, and respiratory tract disease, among others, may potentially have increased of severe adverse reactions following vaccination against COVID-19 and experiencing adverse events.

Sequential provocation of Ekbom's syndrome and acute mania following AstraZeneca COVID-19 vaccination.

ChAdOx1 nCoV-19 vaccine (so called AZ vaccine), is widely used to prevent the SARS-CoV-2 pandemic and shows powerful effectiveness to deter community transmission. There are common immunogenicity-related side effects such as fever, myalgia, lethargy, and headache; however, rare report on the neuropsychiatric problems (Ramasamy et al., 2021). In Taiwan, more than 15,200,000 doses of AZ vaccine were injected by the end of 2022. Here we presented a unique case with separated episode of Ekbom's syndrome, also called delusion of parasitosis, and mania following successive AZ vaccination in three-month interval.

Clinical Effects of BNT162b2 Vaccine on the Short-Term Course of Chronic Spontaneous Urticaria Patients.

Background: The clinical effects of Pfizer-BioNTech coronavirus disease 2019 (COVID-19; BNT162b2) vaccine on the clinical course of chronic spontaneous urticaria (CSU) is unclear. Aims and Objectives: To evaluate the clinical effects of BNT162b2 vaccine on the clinical course of CSU. Methods: In this study, 90 CSU patients vaccinated with one or two repeated doses of BNT162b2 vaccine were included. Urticaria Activity Score over 28 days (UAS28), Urticaria Control Test (UCT), Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL), and Medication Scores (MSs) were obtained before the vaccination, 28 days after the first and, if available, after the second dose of BNT162b2 vaccine. The demographic, clinical, and laboratory features were compared between the subjects with exacerbated (group A) and non-exacerbated (group B) disease activity. Results: Among the 90 study participants, 14 (15.5%) experienced exacerbations in their urticarial activity after the first or repeated doses of BNT162b2 vaccinations. The demographic, clinical, and laboratory features were similar between the exacerbated and non-exacerbated CSU patients. However, the rate of adverse reactions within 48 hours, such as hives, injection site reactions and wheals lasting <1 hour, were significantly higher in group A than in group B (P = 0.004, P < 0.001, P = 0.001, P = 0.018). Conclusions: BNT162b2 vaccination caused an exacerbation in 15.5% of CSU patients during the short-term follow-up. The long-term evaluation can be informative about the lasting effects of BNT162b2 vaccine on the clinical course of CSU patients.

Clinical Phenotypes of Immediate First-Dose Reactions to mRNA COVID-19: A Multicenter Latent Class Analysis.

BACKGROUND: Although immediate potentially allergic reactions have been reported after dose 1 of mRNA coronavirus disease 2019 (COVID-19) vaccines, comprehensively defined subtypes have not been clearly distinguished. OBJECTIVE: To define distinct clinical phenotypes of immediate reactions after dose 1 of mRNA COVID-19 vaccination, and to assess the relation of clinical phenotype to mRNA COVID-19 vaccine second dose tolerance. METHODS: This retrospective study included patients with 1 or more potentially allergic symptoms or signs within 4 hours of receiving dose 1 of an mRNA COVID-19 vaccine and assessed by allergy/immunology specialists from 5 U.S. academic medical centers (January-June 2021). We used latent class analysis-an unbiased, machine-learning modeling method-to define novel clinical phenotypes. We assessed demographic, clinical, and reaction characteristics associated with phenotype membership. Using log-binomial regression, we assessed the relation between phenotype membership and second dose tolerance, defined as either no symptoms or mild, self-limited symptoms resolving with antihistamines alone. A sensitivity analysis considered second dose tolerance as objective signs only. RESULTS: We identified 265 patients with dose-1 immediate reactions with 3 phenotype clusters: (1) Limited or Predominantly Cutaneous, (2) Sensory, and (3) Systemic. A total of 223 patients (84%) received a second dose and 200 (90%) tolerated their second dose. Sensory cluster (all patients had the symptom of numbness or tingling) was associated with a higher likelihood of second dose intolerance, but this finding did not persist when accounting for objective signs. CONCLUSIONS: Three novel clinical phenotypes of immediate-onset reactions after dose 1 of mRNA COVID-19 vaccines were identified using latent class analysis: (1) Limited or Predominantly Cutaneous, (2) Sensory, and (3) Systemic. Whereas these clinical phenotypes may indicate differential mechanistic etiologies or associations with subsequent dose tolerance, most individuals proceeding to their second dose tolerated it.

Aseptic pleocytosis eight days after the first dose of a vector-based SARS-CoV-2 vaccine.

Objectives: Vaccination against SARS-CoV-2 is considered beneficial by the majority, but side effects occur in some cases. Results and Conclusions: We report on a 28-year-old female who developed fever within 3 days of an initial dose with a vector-based SARS-CoV-2 vaccine. Eight days after vaccination, she developed paresthesias and dysesthesias of all four limbs. Cerebral imaging showed two non-specific and non-enhancing lesions in the left white matter. Cerebrospinal fluid (CSF) studies revealed pleocytosis of 82/3 cells. Examination for multiple sclerosis, neuromyelitis optica, acute, demyelinating encephalomyelitis, and Guillain-Barre syndrome was negative. She received steroids, which resulted in complete resolution of the neurological abnormalities. In summary, SARS-CoV-2 vaccination can occasionally be complicated by an inflammatory CSF syndrome, which resolves on administration of steroids.

Examining the association between vaccine reactogenicity and antibody titer dynamics after the third dose of BNT162b2 vaccine using a mixed-effects model

Background: To mitigate the COVID-19 pandemic, many countries have recommended the use of booster vaccinations. The relationship between the degree of adverse vaccine reactions and elevated antibody titers is of interest;however, no studies have investigated the temporal changes in antibody titers based on repeated measurements after a third dose of the BNT162b2 vaccine. Methods: This prospective longitudinal cohort study was conducted with 62 healthcare workers who received a third dose of the BNT162b2 at Okayama University Hospital, Japan. Venous blood draw and fingertip whole blood test sample collection were conducted at the early (3–13 days) and 1-month time points;only FWT sample collection was conducted at the 2-month time point. Information on adverse reactions within 1 week after vaccination was also obtained. The association between fever of 37.5 °C or higher and antibody titers after the third dose of BNT162b2 was examined using a mixed-effects model and Poisson regression with robust variance. Results: A trend toward higher antibody titers in the early period after vaccination was observed in the febrile individuals, but the differences were not significant at 1 and 2 months post-vaccination (the partial regression coefficient for fever was 8094.3 [-1910.2, 18,098.8] at 1 month after vaccination, and 1764.1 [-4133.9, 7662.1] at 2 months after vaccination in the adjusted models). Conclusion: The findings suggest that the presence of fever after the third vaccine does not predict a sustained elevation in serum antibody titers. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases

An observational study of adverse drug reactions to COVID-19 vaccines reported to the New Mexico poison center hotline.

INTRODUCTION: Post-marketing data on coronavirus vaccines are limited. This study evaluated adverse reactions reported to a statewide hotline after the administration of a coronavirus disease-2019 (COVID-19) vaccine. METHODS: We collected reports between 1 December 2020 through 30 August 2021 of any individual 12 years of age and older who received an FDA EUA-approved vaccine and experienced an adverse reaction. For each case, we collected vaccine brand, demographics, adverse reaction type, severity, onset of reaction, duration, and outcome. Relative risk analyses were conducted to investigate factors associated with vaccine adverse reactions. RESULTS: 638 adverse drug reaction cases were recorded. The majority identified as female (70.8%) and the median age was 56. Implicated brands were Pfizer BNT162b2 (46.6%), Moderna mRNA-1273 (43.41%), and Janssen Ad26.COV2.S (8.78%). Although the lowest number of cases was with Janssen, this vaccine had the highest incident rate based on reactions per 100,000 doses. Adverse reactions with the highest incidence were systemic reactions (92.7%), injection-site reactions (8.5%), and local non-injection-site reactions (10.4%), with most judged as minor severity. Relative risk was higher for Moderna compared to Pfizer for injection-site non-severe (RR 2.01) and injection-site severe (RR 1.94) reactions. Janssen had a higher risk of headache, dyspnea, and vision changes compared to Pfizer, and a higher risk of headache compared to Moderna. The relative risk for fever, chills, and lymphadenopathy was higher for the second dose than the first dose for all patients. CONCLUSION: This observational study analyzing adverse drug reactions of the COVID-19 vaccine found that most complaints concerned systemic reactions. We found reaction differences among vaccine brands, between first and second doses for some effects, and selected recurrent events. Poison control centers are uniquely positioned to conduct post-marketing surveillance for the new vaccines as they are available 24/7 to the public and are healthcare providers. Further post-marketing studies are essential to provide a holistic safety profile of COVID-19 vaccines.