key: cord-0955633-7gqwyuhs authors: Sharff, Katie A.; Dancoes, David M.; Longueil, Jodi L.; Johnson, Eric S.; Lewis, Paul F. title: Risk of myopericarditis following COVID‐19 mRNA vaccination in a large integrated health system: A comparison of completeness and timeliness of two methods date: 2022-04-16 journal: Pharmacoepidemiol Drug Saf DOI: 10.1002/pds.5439 sha: 122b960f805151045c3f5790782d35c30171d7b3 doc_id: 955633 cord_uid: 7gqwyuhs 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. 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). 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. COVID-19 vaccination, hospital claims, ICD-10 code, incidence of myopericarditis, myopericarditis, Vaccine Safety Datalink • 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-CM 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 that is higher than the incidence reported to US advisory committees in the fall of 2021. • We encourage other VSD sites to validate the case ascertainment. This report identifies that our encounter methodology identified approximately twice as many cases of myopericarditis following COVID-19 mRNA vaccination than the CDC's Vaccine Safety Datalink. Omissions in ICD-10-CM codes and claims delays were the primary reasons the VSD's search algorithm missed these cases. Days to claim filed measures the number of days between the first clinical encounter for myopericarditis and the outside hospital or clinic filing an insurance claim with KPNW for cases detected by VSD methodology. Realtime surveillance would miss events that were only recognized through delayed insurance claims. For example, patient 7 would not have been identified by an algorithm based on insurance claims for more than 6 months after the onset of myopericarditis (195 days). In contrast, when the myopericarditis was diagnosed at a KPNW-owned hospital or clinic there was no need for an insurance claim to be submitted; those are marked "internal" for encounters within the KPNW integrated delivery system. To reproduce the VSD methodology 2 we restricted our search to select ICD-10-CM discharge codes from emergency department visits and hospitalizations, including hospitals owned by KPNW and hospitals unaffiliated with KPNW, which submit insurance claims to KPNW. Each diagnosis associated with an ICD-10-CM code of B33.22, B33.23, I30,* or I40* was then flagged as meeting the criteria of being identified by the VSD. As above, two physicians independently reviewed the patient records to classify as confirmed, probable or not cases based on the case definition. 5 We calculated the risk per million second doses of vaccine. We stratified the risk by age bands to understand how the risk of myocarditis or pericarditis depended on age. We calculated exact 95% confidence intervals using Stata 17 and the default Clopper-Pearson binomial method. 6 The encounter text description methodology identified 14 distinct We identified a higher estimate of myopericarditis following COVID-19 mRNA vaccine by searching encounter text description of an inte- This outpatient pediatric cardiology appointment occurred at day 25 after his initial presentation. A similar scenario occurred with patient #16 whose initial encounter was diagnosed as Chest Pain (ICD-10-CM code R07.9) which occurred 1 day after vaccination. She had cardiology evaluation >21 days after the initial presentation, and received the more specific code of Pericarditis, Unspecified (ICD-10-CM I31.9). It is unclear why a 21-day cut-off was defined by the VSD and by expanding our search for a relevant diagnosis to 30 days since vaccination, we were able to identify additional events. However, the number of chart reviews to adjudicate the additional cases identified between days 22 through 30 may not merit the associated work burden for this incremental improvement in case ascertainment. Our estimate of the incidence of myopericarditis following COVID-19 mRNA vaccine is similar in magnitude to that reported from studies from Israel and Hong Kong 7-9 but higher than that reported in the US studies and at Vaccines and Related Biological Products Advisory Committee (VRBPAC) and Advisory Committee on Immunization Practices (ACIP) meetings during the fall of 2021. [10] [11] [12] [13] Complete case estimates are essential when modeling risk and benefit for wide-scale vaccine implementation and booster doses in younger age groups. The encounter text description methodology identified approximately twice as many cases of myopericarditis following COVID-19 mRNA vaccination. The VSD is a multi-site consortium with several sites relying on outside claims data to identify cases, potentially resulting in prolonged data lags for accurate ascertainment of events. We would encourage other VSD sites to validate the case ascertainment of the VSD methodology. Future modeling and public policy decisions on vaccine safety should consider the limitations of VSD derived estimates. Surveillance for adverse events after COVID-19 mRNA vaccination Symptomatic acute myocarditis in 7 adolescents after Pfizer-BioNTech COVID-19 vaccination Patients with acute myocarditis following mRNA COVID-19 vaccination Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the advisory committee on immunization practices -United States The use of confidence or fiducial limits illustrated in the case of the binomial Myocarditis after BNT162b2 mRNA vaccine against Covid-19 in Israel Myocarditis after Covid-19 vaccination in a large health care organization Epidemiology of acute myocarditis/pericarditis in Hong Kong adolescents following Comirnaty vaccination Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from Acute myocarditis following COVID-19 mRNA vaccination in adults aged 18 years or older Presentation Slides j Immunization Practices j CDC Proceedings of the Vaccines and Related Biological Products Advisory Committee, 10/26/21. Vaccines and Related Biological Products Advisory Committee October 26, Meeting Announcement Risk of myopericarditis following COVID-19 mRNA vaccination in a large integrated health system: A comparison of completeness and timeliness of two methods All authors declare that they have no conflicts of interest.