Neurological manifestations of acute SARS-CoV-2 infection in pediatric patients: a 3-year study (preprint)

Purpose This study analyzed the neurological manifestation profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across pandemic waves in pediatric patients.Methods This retrospective study analyzed the data of patients aged 0–18 years who were diagnosed with acute SARS-CoV-2 infection and admitted to a pediatric tertiary hospital between March 1, 2020, and February 28, 2023. The presence of neurological manifestations was established based on the symptoms noted in each patient chart. The relationships between neurological manifestations and pandemic waves or age groups were assessed using the chi-square test.Results This study included 1677 patients. Neurological manifestations were noted in 10% (n = 168) of patients with a 3.2 years median age (interquartile range: 1–11.92). Neurological manifestations were significantly associated with the pandemic waves (p = 0.006) and age groups (p < 0.001). Seizures were noted in 4.2% of cases and reached an increasing frequency over time (p = 0.001), but were not associated with age groups. Febrile seizures accounted for the majority of seizures. Headache was reported in 2.6% of cases and had similar frequencies across the pandemic waves and age groups. Muscular involvement was noted in 2% of cases and reached a decreasing frequency over time (p < 0.001) and showed different frequencies among the age groups.Conclusions Neurological manifestations of acute SARS-CoV-2 infection exhibit distinct patterns, depending on the pandemic wave and patient age group. The Wuhan and Omicron waves involved the nervous system more often than the other waves; however, this was probably through different mechanisms.

Evaluation of Febrile Seizure Risk Following Ancestral Monovalent COVID-19 mRNA Vaccination Among U.S. Children Aged 2-5 Years (preprint)

Importance The United States Food and Drug Administration noted a potential safety concern for seizure in children aged 2-5 years receiving the ancestral monovalent COVID-19 mRNA vaccines. Objective To evaluate febrile seizure risk following monovalent COVID-19 mRNA vaccination among children aged 2-5 years. Design, Setting, and Participants The primary analysis evaluated children who had a febrile seizure outcome in the 0-1 days following COVID-19 vaccination. A self-controlled case series analysis was performed in three commercial insurance databases to compare the risk of seizure in the risk interval (0-1 days) to a control interval (8-63 days). Exposure Receipt of dose 1 and/or dose 2 of monovalent COVID-19 mRNA vaccinations. Main Outcomes and Measures The primary outcome was febrile seizure (0-1 day risk interval). Analysis A conditional Poisson regression model was used to compare outcome rates in risk and control intervals and estimate incidence rate ratios (IRR) and 95% confidence intervals (CIs). Meta-analyses were used to pool results across databases. Results The primary meta-analysis found a statistically significant increased incidence of febrile seizure, in the 0-1 days following mRNA-1273 vaccination compared to the control interval (IRR: 2.52, 95% CI: 1.35 to 4.69, risk difference (RD)/100,000 doses = 3.22 (95%CI -0.31 to 6.75)). For the BNT162b2 vaccination, the IRR was elevated but not statistically significant (IRR: 1.41, 95%CI: 0.48 to 4.11, RD/100,000 doses = -0.25 (95%CI -2.75 to 2.24). Conclusions and Relevance Among children aged 2-5 years, the analysis showed a small elevated incidence rate ratio of febrile seizures in the 0-1 days following the mRNA-1273 vaccination. Based on the current body of scientific evidence, the safety profile of the monovalent mRNA vaccines remains favorable for use in young children.

Analysis of risk factors for seizures and short-term reoccurrence of seizures in febrile children with SARS-CoV-2 infection: an observational study (preprint)

Background:With the epidemic of the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) variant Omicron, its accompanying neurological manifestations have gradually attracted attention.The main objective of this study was to compare seizures in febrile children with and without coronavirus disease 2019(COVID-19) and to conduct a short-term follow-up in the COVID-19 positive group to investigate the risk factors for short-term recurrence of seizures in children with febrile seizures(FS). Methods: Retrospective analysis of patients admitted to the Children's Hospital of Chongqing Medical University for fever and seizures between October 1 and December 30, 2022.Based on the results of SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR), the patients were divided into a COVID-19 positive group and a COVID-19 negative group.Moreover,we followed up patients in the COVID-19-positive group for 3 months using outpatient or telephone follow-up, and the main content of follow-up included whether the patients had seizures after discharge and whether there were neurological abnormalities. Results:Compared with the COVID-19-negative group, the COVID-19-positive group had a higher proportion of seizure duration ≥ 15 minutes(18.7%VS5.1%;P=0.001), seizure ≥ 2 time(54.4%VS41.0%;P=0.024), status epilepticus(15.4%VS5.1%;P=0.005), and Electroencephalogram (EEG) abnormalities(29.4%VS13.6%;P=0.016).Seizures ≥2 time[P=0.015,OR(95% CI)=4.632(1.347-15.928)], peak temperature ≤39°C[P=0.001,OR(95% CI)=6.296(2.059-19.254)], and history of convulsions[P=0.005,OR(95% CI)=5.628(1.707-18.550)] were risk factors for recurrence of seizures within a short period of time in children with covid-19 infected febrile convulsions.In the COVID-19 positive group, three patients died and four patients had residual cognitive or motor dysfunction. Conclusions:The seizures were more severe in the COVID-19 positive group compared to the COVID-19 negative group.In addition, patients with COVID-19 who present with seizures and persistent impaired consciousness need to be alerted to serious neurological disorders such as acute necrotizing encephalopathy.

Impact of the Omicron strain on febrile convulsions in children: A single-center observational study (preprint)

<Purpose> The emergence of the Omicron strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of December 2021 has drastically increased the number of infected children in Japan, along with the number of children with febrile convulsions. However, impact of the Omicron strain on the febrile convulsions in children is not clear.<Methods> We compared the frequency of SARS-CoV-2 infection in children hospitalized with febrile convulsions with the frequency of SARS-CoV-2 infection in children with fever and respiratory symptoms without convulsions.<Results> In 2021 and 2022, 49 and 58 children, respectively, required emergency hospitalization for febrile convulsions (FC group), in which 24 and 38 children underwent a Filmarray respiratory panel ® test (FA test) and quantitative antigen test for SARS-CoV-2, respectively. In 2022, only six patients tested positive for SARS-CoV-2 (10.3%, 6/58). As a reference group, 655 children aged < 10 years who underwent the FA test for fever and respiratory symptoms during the same period were investigated, and 4 (1.8%, 4/223) and 42 (9.7%, 42/432) tested positive for SARS-CoV-2 in 2021 and 2022, respectively. Rhinovirus/enterovirus (RV/EV) was the most frequently detected virus, followed by respiratory syncytial virus (RSV) and parainfluenza virus 3 (PI3); no significant difference in the trend of detected viruses was observed between the two groups.<Conclusions> The frequency of febrile convulsions associated with SARS-CoV-2 infection of the Omicron strain in children may be similar to that of other common respiratory viruses.

Comparison of febrile seizures in children with or without coronavirus disease-2019: A single-center observational study.

BACKGROUND: Febrile seizure (FS) is one of the most common neurological manifestations of coronavirus disease-2019 (COVID-19) in children. We compared the clinical characteristics of FS in patients with and without COVID-19 during the pandemic period. METHODS: This retrospective single-center study included patients aged 0-18 years who visited the pediatric emergency department (ED) with FS from January 1, 2022, to April 30, 2022. RESULTS: A total of 186 patients visited the pediatric ED with FS during the study period: 123 (66.1%) were positive for COVID-19 and 63 (33.9%) were negative. Patients with COVID-19 were predominantly male (70.7% vs. 50.8%, p = 0.007) and older (2.4 vs. 1.8 years, p = 0.005) than those without COVID-19. A higher proportion of patients with COVID-19 were of atypical age (age > 5 years or <6 months) than those without COVID-19 (26.8% vs. 9.5%, p = 0.006). This was especially true for those aged >5 years (22% vs. 4.8%, p = 0.003). Patients with COVID-19 had a higher probability of multiple episodes of convulsion within 24 h than those without COVID-19 (10.6% vs. 1.6%, p = 0.037). Among patients with COVID-19, males had a shorter fever-to-seizure duration than females (3 h vs. 6.5 h, p = 0.045). CONCLUSIONS: Patients with FS with COVID-19 tend to be predominantly male and have older age of onset than those without COVID-19. Because of the atypical age of onset and probability of multiple convulsion episodes, vigilance for FS is needed in patients with COVID-19, especially males.

The Association Between COVID-19 and Febrile Seizure: A Retrospective Case-Control Study.

BACKGROUND/OBJECTIVE: Throughout the pandemic, febrile seizures have resulted from infection secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The objective of this study is to determine if there is an increased association between COVID-19 and febrile seizures as compared with other causes of febrile seizures. METHODS: This was a retrospective case control study. Data were collected from the National Institute of Health (NIH) supported National COVID Cohort Collaborative (N3C). Patients from 6 to 60 months who were tested for COVID-19 were included; cases were defined as COVID-19-positive patients whereas controls were defined as COVID-19-negative patients. Febrile seizures diagnosed within 48 hours of the COVID-19 test were considered to be associated with the test result. Patients were subjected to a stratified gender and date matching design followed by a logistic regression controlling for age and race. RESULTS: During the study period, 27,692 patients were included. Of those, 6923 patients were COVID-19-positive, among which 189 had febrile seizures (2.7%). After logistic regression, the likelihood of having febrile seizures concurrently with COVID-19 as compared with other causes was 0.96 ( P = 0.949; confidence interval, 0.81, 1.14). CONCLUSIONS: There were 2.7% of the patients with COVID-19 that were diagnosed with a febrile seizure. However, when subjected to a matched case control design with logistic regression controlling for confounding variables, there does not appear to be an increased risk of febrile seizures secondary to COVID-19 as compared with other causes.

Comparison of Clinical Characteristics of Children Infected With Coronavirus Disease 2019 Between Omicron Variant BA.5 and BA.1/BA.2 in Japan.

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has dramatically altered the clinical profile of pediatric coronavirus disease 2019 (COVID-19). In Japan, we experienced a pandemic of omicron subvariant BA.1/BA.2 from January through June 2022. However, after the emergence of BA.5 in early July 2022, the number of children hospitalized with COVID-19 increased dramatically in Japan. METHODS: We collected data on monthly numbers of cases and clinical characteristics of hospitalized children with COVID-19 in 13 hospitals, the total number of pediatric COVID-19 cases, and COVID-19 vaccination rates in Niigata, Japan, for the period from January 2020 through August 2022. We compared clinical presentation during the periods of BA.1/BA.2 predominance (January-June 2022) and BA.5 predominance (July-August 2022) and estimated vaccine effectiveness (VE) against hospitalization during the BA.5-predominant period. RESULTS: Between January 1, 2020, and August 31, 2022, 49,387 children (19,085 children/100,000 population) were newly diagnosed as having COVID-19, and 393 were hospitalized for COVID-19. Hospitalization for febrile seizure, especially complex seizure, was significantly higher during BA.5 predominance than during BA.1/BA.2 predominance (27.9% vs. 7.0%, P < 0.01). VE against hospitalization during BA.5 predominance was estimated to be 75% (95% confidence interval, 48%-88%, P < 0.01). CONCLUSIONS: The emergence of BA.5 significantly affected children in Japan; the number with complex febrile seizure who required hospitalization was higher than during BA.1/BA.2 predominance. The COVID-19 vaccination rate in children must be increased to prevent hospitalization for COVID-19 and to prepare for current and future variant outbreaks.

Clinical Analysis of Febrile Seizures in Children with COVID-19 in the Omicron Era: a Single-Center Retrospective Observational Study (preprint)

Objectives：This study sought to investigate the characteristics of febrile seizures in children infected with the Omicron variant in Chongqing province, west of China, and underscore the importance of monitoring for potential neurological complications associated with this variant. Methods: This retrospective study enrolled a total of 84 pediatric patients with COVID-19 and FS who were admitted to Chongqing University Three Gorges Hospital between December 11th and December 26th, 2022. Demographic, clinical, laboratory, radiological and EEG data were retrospectively summarized. Results: The study enrolled 84 children, with a median age of 21.5 (15-35.5) months and a range of 6-162 months. Among these, 11.9% were of atypical age (age > 5 years). The patient population comprised of 54 (64.29%) boys and 30 (35.71%) girls. 32.14% presented with complex FS. Generalized tonic-clonic seizures occurred in 51.19%, followed by generalized tonic seizures (43.43%). 86.9% occurred within 24h after fever onset and 80.95% continued for ≤ 5min. Conclusions: Febrile seizures in children with Omicron VOC are common COVID-19 illness with a higher prevalence compared with other VOCs. They present with similar clinical manifestations and resolve spontaneously with a benign clinical outcome in line with other seasonal viruses.

The Impact of Omicron Wave on Pediatric Febrile Seizure.

BACKGROUND: The coronavirus disease 2019 (COVID-19) omicron (B.1.1.529) variant reduced the risk of severe disease compared with the original strain and other variants, but it appeared to be highly infectious, which resulted in an exponential increase in confirmed cases in South Korea. As the number of confirmed cases increased, so did the number of pediatric patients' hospitalization. This study aims to evaluate the frequency and clinical features of febrile seizure associated with the COVID-19 omicron variant in children. METHODS: We retrospectively reviewed the medical records of children aged under 18 years with febrile seizure who were tested for COVID-19 from February 2020 to April 2022 at Ajou University Hospital, South Korea. Based on the dominant variants, we divided the period into the pre-omicron (from February 2020 to December 2021) and omicron periods (from January 2022 to April 2022) and compared the clinical characteristics between the two. Also, we compared the clinical characteristics of febrile seizure between COVID-19 positive and negative group during the omicron period. RESULTS: Among the 308 children, 211 patients (9.2 patients/months) and 97 patients (24.3 patients/months) were grouped into pre-omicron and omicron periods, respectively. Compared with the pre-omicron period, patients in the omicron period showed significantly higher mean age (pre-omicron vs. omicron, 22.0 vs. 28.0 months; P = 0.004) and COVID-19 positive results (pre-omicron vs. omicron, 0.5% vs. 62.9%; P < 0.001). As the COVID-19 confirmed cases in the omicron period increased, the number of COVID-19 associated febrile seizure also increased. In the omicron period, 61 children were confirmed to be positive for COVID-19, and COVID-19 positive group showed statistically significant higher mean age (positive vs. negative, 33.0 vs. 23.0 months; P = 0.003) and peak body temperature than the negative group (positive vs. negative, 39.1°C vs. 38.6°C; P = 0.030). Despite the lack of significance, COVID-19 positive group showed longer seizure time, multiple seizure episodes, and higher prevalence of complex febrile seizure. CONCLUSION: The frequency of COVID-19 associated febrile seizure increased in the omicron periods. In addition, in this period, children with febrile seizure diagnosed with COVID-19 had a higher mean age and higher peak body temperature.

Analysis of inflammatory markers and electroencephalogram findings in paediatric patients with COVID-19: a single-centre study in Korea (preprint)

A big infectious wave overwhelmingly spread from February 2022 in South Korea after the COVID-19 outbreak was managed. Therefore, we analysed electroencephalogram (EEG) findings and serologic inflammatory markers in pediatric patients with COVID-19 by retrospectively reviewing medical records of 41 patients who visited Gyeongsang National University Changwon Hospital from March to May 2022 and were diagnosed with COVID-19; all serologic tests were performed within 24 hours after presenting with fever or seizure. The median patient age and average number of hospitalisation days were 3.6 (0.08–14.00) years and 3.71 (1.0–7.0) days, respectively. Interleukin-6 (IL-6) were elevated above the normal range in all patients (median value, 43.18 [7.0–190.0] pg/ml) and were higher among patients with seizures. Among 41 patients, 17 (41.5%) with a mean age of 5.4 years had higher complaints of seizures. Three patients had prolonged seizures for > 30 minutes and received intravenous lorazepam injections and eight had a complex type of febrile convulsion. Nine patients underwent EEG, and five showed abnormal findings in the initial EEG. In the linear regression model, serum IL-6 and blood lymphocyte counts were correlated with prolonged seizure duration. These findings underscore that several immune cascade-related serologic markers were elevated in children with COVID-19-related febrile seizures. We may assume that COVID-19 presents similarities and differences in the mechanisms that provoke seizures and fever in children.

Serum Glucose and Electrolyte Levels in Children with and without Febrile Seizures: A case-control study (preprint)

Background: Febrile seizures (FS) occur in children aged six to sixty months with a febrile illness not associated with a central nervous system infection or metabolic disorder. Risk factors include; age, history of the disease, certain vaccinations, or iron and zinc deficiencies. Studies show significant hyponatremia, hypocalcemia, and hyperkalemia in children with febrile seizures. Similarly, cerebrospinal fluid hyperglycemia is common in febrile convulsions. This study aimed to retrospectively assess the relationship between febrile seizures, and electrolyte & glucose imbalance among children with fever, and also compare the annual trends of febrile seizure-related admissions pre- and post-Covid 19 pandemics. Methods:  A case-control study was conducted from January 2018 to January 2022 at Zhongnan Hospital of Wuhan University, Hubei, China. 876 children aged 6 to 60 months were divided into 438 cases with febrile seizures (cases) and 438 with fever but without seizures (controls). Serum glucose and electrolyte levels at the time of hospitalization as well as age, gender, birth weight, gestational age, temperature, and causes of fever, in both groups were retrieved, analyzed, and compared. Results: Febrile seizure admissions among children aged 6-60 months were significantly reduced to less than 23.4% during the Covid-19 pandemic. Children with febrile seizures had significantly higher serum glucose levels than those with fever but without seizures (p < 0.05). The serum sodium levels of children with seizures were significantly lower than those without seizures (p < 0.05). Sodium levels were significantly lower among children with complex seizures (p < 0.05). There was no significant difference in the serum electrolyte levels of potassium and calcium between the cases and controls (p > 0.05). A significant positive correlation was found between serum sodium levels and the occurrence of febrile seizures (r = [0.156]; p < 0.05). Conclusion: The study found that admission rates for febrile seizures decreased during Covid-19 and lower sodium levels could be a risk factor for the occurrence of febrile seizures.

Background incidence rates of adverse events of special interest related to COVID-19 vaccines in Ontario, Canada, 2015 to 2020, to inform COVID-19 vaccine safety surveillance.

BACKGROUND: Background incidence rates are critical in pharmacovigilance to facilitate identification of vaccine safety signals. We estimated background incidence rates of 11 adverse events of special interest related to COVID-19 vaccines in Ontario, Canada. METHODS: We conducted a population-based retrospective observational study using linked health administrative databases for hospitalizations and emergency department visits among Ontario residents. We estimated incidence rates of Bell's palsy, idiopathic thrombocytopenia, febrile convulsions, acute disseminated encephalomyelitis, myocarditis, pericarditis, Kawasaki disease, Guillain-Barré syndrome, transverse myelitis, acute myocardial infarction, and anaphylaxis during five pre-pandemic years (2015-2019) and 2020. RESULTS: The average annual population was 14 million across all age groups with 51% female. The pre-pandemic mean annual rates per 100,000 population during 2015-2019 were 191 for acute myocardial infarction, 43.9 for idiopathic thrombocytopenia, 28.8 for anaphylaxis, 27.8 for Bell's palsy, 25.0 for febrile convulsions, 22.8 for acute disseminated encephalomyelitis, 11.3 for myocarditis/pericarditis, 8.7 for pericarditis, 2.9 for myocarditis, 2.0 for Kawasaki disease, 1.9 for Guillain-Barré syndrome, and 1.7 for transverse myelitis. Females had higher rates of acute disseminated encephalomyelitis, transverse myelitis and anaphylaxis while males had higher rates of myocarditis, pericarditis, and Guillain-Barré syndrome. Bell's palsy, acute disseminated encephalomyelitis, and Guillain-Barré syndrome increased with age. The mean rates of myocarditis and/or pericarditis increased with age up to 79 years; males had higher rates than females: from 12 to 59 years for myocarditis and ≥12 years for pericarditis. Febrile convulsions and Kawasaki disease were predominantly childhood diseases and generally decreased with age. CONCLUSIONS: Our estimated background rates will permit estimating numbers of expected events for these conditions and facilitate detection of potential safety signals following COVID-19 vaccination.

Vaccination and childhood epilepsies.

INTRODUCTION: The evidence relating vaccination to febrile seizures and epilepsy is evaluated with an emphasis on febrile seizures (FS), Dravet syndrome (DS), West syndrome, and other developmental and epileptic encephalopathies. METHODS: A systematic literature review using search words vaccination/immunization AND febrile seizures/epilepsy/Dravet/epileptic encephalopathy/developmental encephalopathy was performed. The role of vaccination as the cause/trigger/aggravation factor for FS or epilepsies and preventive measures were analyzed. RESULTS: From 1428 results, 846 duplicates and 447 irrelevant articles were eliminated; 120 were analyzed. CONCLUSIONS: There is no evidence that vaccinations cause epilepsy in healthy populations. Vaccinations do not cause epileptic encephalopathies but may be non-specific triggers to seizures in underlying structural or genetic etiologies. The first seizure in DS may be earlier in vaccinated versus non-vaccinated patients, but developmental outcome is similar in both groups. Children with a personal or family history of FS or epilepsy should receive all routine vaccinations. This recommendation includes DS. The known risks of the infectious diseases prevented by immunization are well established. Vaccination should be deferred in case of acute illness. Acellular pertussis DTaP (diphtheria-tetanus-pertussis) is recommended. The combination of certain vaccine types may increase the risk of febrile seizures however the public health benefit of separating immunizations has not been proven. Measles-containing vaccine should be administered at age 12-15 months. Routine prophylactic antipyretics are not indicated, as there is no evidence of decreased FS risk and they can attenuate the antibody response following vaccination. Prophylactic measures (preventive antipyretic medication) are recommended in DS due to the increased risk of prolonged seizures with fever.

Evaluation of Febrile Seizure Diagnoses Associated With COVID-19.

BACKGROUND/OBJECTIVES: Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be associated with febrile seizures, but the overall frequency and outcomes are unknown. The objectives of this study are to (1) determine the frequency of pediatric subjects diagnosed with febrile seizures and COVID-19, (2) evaluate patient characteristics, and (3) describe the treatments (medications and need for invasive mechanical ventilation) applied. METHODS: This was a retrospective study utilizing TriNetX electronic health record data. We included subjects ranging from 0 to 5 years of age with a diagnosis of febrile seizures (R56.00, R56.01) and COVID-19 (U07.1). We extracted the following data: age, race, ethnicity, diagnostic codes, medications, laboratory results, and procedures. RESULTS: During this study period, 8854 pediatric subjects aged 0-5 years were diagnosed with COVID-19 among 34 health care organizations and 44 (0.5%) were also diagnosed with febrile seizures (simple, 30 [68.2%]; complex, 14 [31.8%]). The median age was 1.5 years (1, 2), there were no reported epilepsy diagnoses, and a proportion required hospitalization (11; 25.0%) and critical care services (4; 9.1%). CONCLUSIONS: COVID-19 infections in children can be associated with febrile seizures. In our study, 0.5% of COVID-19 subjects were diagnosed with febrile seizures and approximately 9% of subjects were reported to require critical care services. Febrile seizures, although serious, are not a commonly diagnosed neurologic manifestation of COVID-19.

Convulsions in children with COVID-19 during the Omicron wave.

AIM: Most children with COVID-19 have mild symptoms, but data on the Omicron variant are rare. This paper describes unexpected cases with convulsions during 1 week in January 2022. METHODS: Four children with COVID-19 were admitted with convulsions to the paediatric department in Örebro, Sweden, when Omicron accounted for more than 98% of the country's COVID-19 cases. Three children tested positive for the virus, and one had clinical COVID-19. I was able to contact the parents of three boys, who gave consent for these case studies. RESULTS: Two boys aged 3 and 21 months tested positive for the virus and a 14-year-old boy tested negative, but had a cold and family members who had tested positive. The teenager had a history of urinary tract infections, but the younger boys had no earlier comorbidities. None had a history of epilepsy or febrile convulsions. The younger children had a fever and the teenager had upper respiratory symptoms. The 3-month-old child had repeated convulsions for several hours, the 21-month-old had continuous convulsions for 15-20 min, and the teenager had a convulsion for 30-60 s, followed by uncharacteristic aggression. CONCLUSION: Convulsions may be a sign of the Omicron variant in children with COVID-19.

Background incidence rates of adverse events of special interest related to COVID-19 vaccines in Ontario, Canada, 2015 to 2020, to inform COVID-19 vaccine safety surveillance (preprint)

Background: Background incidence rates are critical in pharmacovigilance to facilitate identification of vaccine safety signals. We estimated background incidence rates of nine adverse events of special interest related to COVID-19 vaccines in Ontario, Canada. Methods: We conducted a population-based retrospective observational study using linked health administrative databases for hospitalizations and emergency department visits among Ontario residents. We estimated incidence rates of Bells palsy, idiopathic thrombocytopenia, febrile convulsions, acute disseminated encephalomyelitis, myocarditis, pericarditis, Kawasaki disease, Guillain-Barre syndrome, and transverse myelitis during five pre-pandemic years (2015-2019) and 2020. Results: The average annual population was 14 million across all age groups with 51% female. The pre-pandemic mean annual rates per 100,000 population during 2015-2019 were 43.9 for idiopathic thrombocytopenia, 27.8 for Bells palsy, 25.0 for febrile convulsions, 22.8 for acute disseminated encephalomyelitis, 11.3 for myocarditis/pericarditis, 8.6 for pericarditis, 2.9 for myocarditis, 1.9 for Guillain-Barre syndrome, 1.7 for transverse myelitis, and 1.6 for Kawasaki disease. Females had higher rates of acute disseminated encephalomyelitis and transverse myelitis while males had higher rates of myocarditis, pericarditis, and Guillain-Barre syndrome. Bells palsy, acute disseminated encephalomyelitis, and Guillain-Barre syndrome increased with age. The mean rates of myocarditis and/or pericarditis increased with age up to 79 years; males had higher rates than females: from 12-59 years for myocarditis and 12 years and older for pericarditis. Febrile convulsions and Kawasaki disease were predominantly childhood diseases and generally decreased with age. Conclusions: Our estimated background rates will permit estimating numbers of expected events for these conditions and facilitate detection of potential safety signals following COVID-19 vaccination.

Linking Physical Activity to Personal Values: Feasibility and Acceptability Randomized Pilot of a Behavioral Intervention for Older Adults with Osteoarthritis Pain (preprint)

Background: Osteoarthritis (OA) pain is common and leads to functional impairment for many older adults. Physical activity can improve OA outcomes for older adults, but few are appropriately active. Behavioral interventions can reduce barriers to physical activity. We developed and tested a brief, novel behavioral intervention for older adults combining values to enhance motivation and strategic activity pacing to improve arthritis-related pain and functioning and increase physical activity. Methods A randomized feasibility and acceptability pilot trial compared Engage-PA to treatment as usual plus fitness tracker (TAU+) in N=40 adults age 65+ with OA pain in the knee or hip. Engage-PA involved two 60-minute telephone sessions. All participants wore a fitness tracker to collect daily steps throughout the study and completed baseline and post-treatment assessments of secondary outcomes (arthritis-related pain and physical functioning, physical activity, psychological distress, psychological flexibility, and value-guided action). The impact of COVID-19 on general wellbeing and physical activity was also assessed. Descriptive statistics were conducted for feasibility and acceptability outcomes. Indicators of improvement in secondary outcomes were examined via change scores from baseline to post-treatment and performing independent samples t -tests to assess for between-group differences. Results Feasibility was high; 100% accrual, low (5%) attrition, and 100% completion of study sessions. Acceptability was high, with 89% finding the intervention “mostly” or “very” helpful. Engage-PA participants demonstrated improvements in arthritis pain severity ( M diff =1.68, p

Adverse events of special interest for COVID-19 vaccines - background incidences vary by sex, age and time period and are affected by the pandemic (preprint)

Background With large-scale COVID-19 vaccination implemented world-wide, safety signals needing rapid evaluation will emerge. We report population-based, age- and-sex-specific background incidence rates of conditions representing potential vaccine adverse events of special interest (AESI) for the Swedish general population using register data. Methods We studied an age/sex-stratified random 10% sample of the Swedish population on 1 Jan 2020, followed for AESI outcomes during 1 year, as the COVID-19 pandemic emerged and developed, before the start of vaccinations. We selected and defined the following outcomes based on information from regulatory authorities, large-scale adverse events initiatives and previous studies: aseptic meningitis, febrile seizure, Kawasaki syndrome, MISC, post-infectious arthritis, arthritis, myocarditis, ARDS, myocardial infarction, stroke, ischemic stroke, hemorrhagic stroke, venous thromboembolism, pulmonary embolism, kidney failure, liver failure, erythema multiforme, disseminated intravascular coagulation, autoimmune thyroiditis, and appendicitis. We calculated incidence rates stratified by age, sex and time period (quarters of 2020), and classified them using Council of International Organizations of Medical Sciences (CIOMS) categories: very common, common, uncommon, rare, or very rare. Results We included 972,723 study subjects, representing the Swedish national population on 1 Jan 2020. We found that AESI incidence rates vary greatly by age and in some cases sex. Several common AESIs showed expected increase with age, while some (e.g. appendicitis, aseptic meningitis, autoimmune thyroiditis, Kawasaki syndrome and MISC) were more common in young people, and others exhibited a flatter age pattern (e.g. myocarditis, DIC and erythema multiforme). Consequently, the CIOMS classification for AESIs varied widely according to age. Considerable variability was suggested for some AESI rates across the 4 quarters of 2020, potentially related to pandemic waves, seasonal variation, healthcare system overload or other healthcare delivery effects. Conclusion Age, sex, and timing of rates are important to consider when background AESI rates are compared to corresponding rates observed with COVID-19 vaccines.