Katie A. Sharff

Purpose: What is the absolute occurrence of ischemic stroke and transient ischemic attack after a COVID-19 bivalent vaccination? Methods: We conducted a retrospective cohort study of Kaiser Permanente Northwest (KPNW) patients 18 years and older who were vaccinated with either the Pfizer or Moderna formulation of the COVID-19 bivalent vaccine between September 1, 2022 and March 1 ^st 2023. Patients were included in the study if they had KP membership at the time of vaccination and through the 21-day follow up period. We replicated the Vaccine Safety Datalink (VSD) rapid cycle analysis methodology and searched for possible cases of ischemic stroke or TIA in the 21 days following vaccination using ICD-10-CM diagnosis codes in both the primary position and any position. We waited 90 days from the end of the follow up (March 21, 2023) for complete non-KP data accrual before analyzing the data to account for the lag in processing outside hospital insurance claims. Two physicians adjudicated possible cases by reviewing the clinical notes in the electronic health record. The analyses were stratified by age ≥65 years to allow for comparisons with VSD’s reporting at the Advisory Committee on Immunization Practices (ACIP) meeting of incidence of ischemic stroke or TIA (VSD reported incidence; 24.6 cases of ischemic stroke or TIA per 100,000 patients vaccinated). Results: The incidence of ischemic stroke or TIA was 34.3 per 100,000 (95% CI, 17.7 – 59.9) in patients 65 years or older who received the bivalent Pfizer vaccine—based on a diagnosis code in the primary position of the emergency department or hospital discharge. The incidence increased to 45.7 per 100,000 (95% CI 26.1 – 74.2) when we expanded the search to a diagnosis in any position and did not adjudicate to confirm. However, most of those additional apparent stroke or TIA diagnoses were false-positive diagnoses based on physicians’ adjudications. Estimating the incidence based on the primary position agreed closely with estimating the incidence based on any position and physician adjudication: 37.1 per 100,000 (95% CI 19.8 – 63.5). Seventy-nine percent of the ischemic stroke cases were admitted to hospitals that are not owned by the integrated delivery system. Conclusion: We identified a 50% increase in the incidence of ischemic stroke per 100,000 patients ages 65 and older vaccinated with the Pfizer bivalent vaccine, compared to the data presented by the VSD. Seventy-nine percent of the ischemic stroke cases were admitted to non-plan hospitals and a delay in processing outside hospital insurance claims was likely responsible for the discrepancy in case ascertainment of ischemic stroke. Physician adjudication of all cases in this study allowed accurate absolute incidence estimates of stroke per 100,000 vaccine recipients and is helpful in calculation of net benefit for policy recommendations and shared decision-making. 5 key points: We identified a 50% increase in incidence of ischemic stroke or transient ischemic attack (TIA) per 100,000 patients ages 65 and older vaccinated with the Pfizer bivalent vaccine, compared to the data presented by the Vaccine Safety Datalink (VSD). Seventy-nine percent of the ischemic stroke and TIA cases were admitted to hospitals that are not owned by the integrated delivery system. A delay in processing outside hospital insurance claims was likely responsible for the discrepancy in case ascertainment of ischemic stroke. Replication of the VSD case definition confirmed the exceptionally high positive predictive value (PPV) in identifying ischemic stroke or TIA within 21 days of Pfizer bivalent vaccination in individuals 65 years and older when the ICD-10-CM hospital discharge code is restricted to the primary position. Physician adjudication of all cases in this study allowed accurate absolute incidence estimates of stroke per 100,000 vaccine recipients and is helpful in calculation of net benefit for policy recommendations and shared decision-making.

Purpose: The JYNNEOS vaccine is an FDA-approved vaccine indicated for prevention of smallpox and monkeypox that is currently being distributed to high-risk individuals to combat the monkeypox public health emergency. The FDA safety data for JYNNEOS vaccine notes potential cardiac adverse events of special interest (AESI) following vaccination. The Advisory Committee on Immunization Practices (ACIP) stated that people with underlying heart disease or three or more major cardiac risk factors should be counseled about the theoretical risk for myopericarditis following vaccination with JYNNEOS. Our objective was to describe the incidence of cardiac AESIs in the Kaiser Permanente Northwest (KPNW) population who received a JYNNEOS vaccination for prevention of monkeypox. Methods: We conducted a retrospective cohort study of 2,126 KPNW patients aged 12 or older who were vaccinated with at least 1 dose of JYNNEOS vaccine between July 14 ^th 2022 and October 10 ^th 2022. We searched KPNW databases, including the electronic health record (EHR), for diagnoses of elevated troponins, chest pain, myocarditis, pericarditis, myopericarditis, acute myocardial infarction, cardiac dysrhythmia, cardiac arrest, or ventricular fibrillation that were documented during any encounter (visit) using ICD-10-CM diagnosis codes. Two KPNW physicians reviewed all possible cases in the EHR to adjudicate cases as cardiac AESIs in alignment with the case definition used in the FDA safety data. Results: There were 2,126 KPNW members who received a total of 3,235 JYNNEOS vaccine doses between July 14 ^th and October 10 ^th . Encounter ICD10 diagnosis codes and troponin values identified 24 possible cardiac AESI cases. After physician adjudication, there were 10 confirmed cardiac AESI for an incidence of 3.1 per 1000 doses given with (exact 95% CI, 1.5 to 5.7). Of these 10 events, none could be attributed directly to the vaccination. Conclusion: The incidence of cardiac adverse events following JYNNEOS vaccination for prevention of monkeypox is unknown and this is the first study to evaluate cardiac AESI following JYNNEOS vaccination in the 2022 monkeypox public health emergency. This retrospective cohort study of JYNNEOS vaccination for prevention of monkeypox identified 10 cardiac events that all had alternative explanations; and no hospitalizations or serious adverse outcomes were attributed to vaccination. This initial study provides timely information for the clinician counseling their patient with underlying cardiac risk factors on the low observed risk of cardiac events with JYNNEOS vaccination during the 2022 monkeypox public health emergency.

Purpose: How completely do hospital discharge diagnoses identify cases of myopericarditis after an mRNA vaccine?Methods: We assembled a cohort 12–39 year‐old patients, insured by Kaiser Permanente Northwest, who received at least one dose of an mRNA vaccine (Pfizer‐BioNTech or Moderna) between December 2020 and October 2021. We followed them for up to 30 days after their second dose of an mRNA vaccine to identify encounters for myocarditis, pericarditis or myopericarditis. We compared two identification methods: A method that searched all encounter diagnoses using a brief text description (e.g., ICD‐10‐CM code I40.9 is defined as ‘acute myocarditis, unspecified’). We searched the text description of all inpatient or outpatient encounter diagnoses (in any position) for “myocarditis” or “pericarditis.” The other method was developed by the Centers for Disease Control and Prevention's Vaccine Safety Datalink (VSD), which searched for emergency department visits or hospitalizations with a select set of discharge ICD‐10‐CM diagnosis codes. For both methods, two physicians independently reviewed the identified patient records and classified them as confirmed, probable or not cases using the CDC's case definition.Results: The encounter methodology identified 14 distinct patients who met the confirmed or probable CDC case definition for acute myocarditis or pericarditis with an onset within 21 days of receipt of COVID‐19 vaccination. When we extended the search for relevant diagnoses to 30 days since vaccination, we identified two additional patients (for a total of 16 patients) who met the case definition for acute myocarditis or pericarditis, but those patients had been misdiagnosed at the time of their original presentation. Three of these patients had an ICD‐10‐CM code of I51.4 “Myocarditis, Unspecified;” that code was omitted by the VSD algorithm (in the late fall of 2021). The VSD methodology identified 11 patients who met the CDC case definition for acute myocarditis or pericarditis. Seven (64%) of the 11 patients had initial care for myopericarditis outside of a KPNW facility and their diagnosis could not be ascertained by the VSD methodology until claims were submitted (median delay of 33 days; range of 12–195 days). Among those who received a second dose of vaccine (n = 146 785), we estimated a risk as 95.4 cases of myopericarditis per million second doses administered (95% CI, 52.1–160.0).Conclusion: We identified additional valid cases of myopericarditis following an mRNA vaccination that would be missed by the VSD's search algorithm, which depends on select hospital discharge diagnosis codes. The true incidence of myopericarditis is markedly higher than the incidence reported to US advisory committees in the fall of 2021. The VSD should validate its search algorithm to improve its sensitivity for myopericarditis.

Purpose: The risk of myopericarditis following COVID-19 booster vaccination has not been extensively evaluated. We provide a timely case ascertainment of myocarditis following COVID-19 booster vaccine in individuals age 18-39 years from an integrated health system. Methods: We studied a cohort of 65,785 Kaiser Permanente (KP) Northwest Health Plan members aged 18-39 years who received a COVID-19 vaccine booster at least 5 months following completion of the primary series. We identified cases of myopericarditis by searching the electronic health record for the National Center for Health Statistics (NCHS) text label for ‘myocarditis’ or ‘pericarditis’ diagnosis codes in all inpatient and outpatient encounters through January 18 ^th 2022. The cohort was followed for 21 days after their booster. We excluded anyone with a documented diagnosis of myocarditis or pericarditis before their first COVID-19 vaccination. Two physicians independently reviewed the identified patient records and applied the CDC myocarditis and pericarditis surveillance case definition to classify records as confirmed, probable or excluded based on the prior published definition. Results: Our method identified 6 patients who met the confirmed or probable CDC case definition for acute myocarditis or pericarditis within 21 days of COVID-19 booster dose among 65,785 eligible members. Four cases occurred in 27,253 men. Overall, we estimated 9.1 cases (exact 95% CI 3.4 to 19.9) of post-booster myopericarditis per 100,000 booster doses given. In men, we estimated 14.7 cases (exact 95% CI 4.0 to 37.6) per 100,000 booster doses given. Conclusion: We identified a rate of 9.1 cases of myopericarditis per 100,000 COVID-19 booster doses which is higher than prior estimates reported by the Vaccine Adverse Event Reporting System (VAERS). Myopericarditis occurs following COVID-19 booster vaccine and may be underreported by current surveillance methods. High sensitivity of these case estimates is essential when modeling risk and benefit for sequential COVID-19 vaccinations for the general population.

Purpose: How completely do hospital discharge diagnoses identify cases of myopericarditis after an mRNA vaccine? Methods: We assembled a cohort 12 to 39 years old patients, insured by Kaiser Permanente Northwest, who received at least one dose of an mRNA vaccine (Pfizer-BioNTech or Moderna) between December 2020 and October 2021. We followed them for up to 30 days after their second dose of an mRNA vaccine to identify encounters for myocarditis, pericarditis or myopericarditis. We compared two identification methods: A method that searched all encounter diagnoses using a brief text description (e.g., ICD-10-CM code I40.9 is defined as ‘acute myocarditis, unspecified’). We searched the text description of all inpatient or outpatient encounter diagnoses (in any position) for “myocarditis” or “pericarditis.” The other method was developed by the Centers for Disease Control and Prevention’s Vaccine Safety Datalink (VSD), which searched for emergency department visits or hospitalizations with a select set of discharge ICD-10-CM diagnosis codes. For both methods, two physicians independently reviewed the identified patient records and classified them as confirmed, probable or not cases using the CDC’s case definition. Results: The encounter methodology identified 14 distinct patients who met the confirmed or probable CDC case definition for acute myocarditis or pericarditis with an onset within 21 days of receipt of COVID-19 vaccination. Three of these 14 patients had an ICD-10 code of I51.4 “Myocarditis, Unspecified” which was overlooked by the VSD algorithm. The VSD methodology identified 11 patients who met the CDC case definition for acute myocarditis or pericarditis. Seven (64%) of the eleven patients had initial care for myopericarditis outside of a KPNW facility and their diagnosis could not be ascertained by the VSD methodology until claims were submitted (median delay of 33 days; range of 12-195 days). Among those who received a second dose of vaccine (n=146,785), we estimated a risk as 95.4 cases of myopericarditis per million second doses administered (95% CI, 52.1 to 160.0). Conclusion: We identified additional valid cases of myopericarditis following an mRNA vaccination that would be missed by the VSD’s search algorithm, which depends on select hospital discharge diagnosis codes. The true incidence of myopericarditis is markedly higher than the incidence reported to US advisory committees. The VSD should validate its search algorithm to improve its sensitivity for myopericarditis. Key Points: We identified a higher estimate of myopericarditis following COVID-19 mRNA vaccine by searching encounter text description compared with the Vaccine Safety Datalink (VSD) methodology An incomplete list of ICD-10 codes and delays in hospital claims data were responsible for the difference We estimated a risk of 95.4 cases of myopericarditis per million second doses administered in patients age 12-39 which is higher than the incidence reported to US advisory committees We encourage other VSD sites to validate the case ascertainment of current VSD methodology