INTRODUCTION: Varicella-zoster virus (VZV) testing is increasingly needed for assessing immunity and diagnosis in the varicella vaccination era. VZV-specific immunoglobulin G (IgG) is recommended when assessing immunity; real-time polymerase chain reaction (PCR) is recommended for varicella or herpes zoster diagnosis. The study objective was to describe VZV serologic and virologic testing in U.S. clinical practice. METHODS: Patients with serologic (IgG, IgM) or virologic (PCR, culture) VZV testing were identified in five administrative data sources (∼11-100 million enrollees; 2016-2023). Descriptive analyses were used to examine VZV testing frequency, patient characteristics, and rates by test type. The top 20 diagnostic codes associated with VZV test type were used as a proxy for reason for testing. RESULTS: Across data sources, the highest proportion of VZV testing was for IgG (43%-92%); most was in females (79%-82%) and those aged 20-39 years (62%-70%). Rates of serologic testing were 50-60/10,000 persons. Frequency of VZV virologic testing was considerably lower; PCR testing rates were ∼1/10,000 persons. Diagnostic codes associated with IgG or virologic testing were primarily categorized as routine care or acute illness, respectively. IgM testing was up to 11% of tests, despite not being recommended for screening or diagnostic purposes. CONCLUSIONS: VZV serologic testing rates were 50-60 times higher than PCR. Serologic testing was more common among females and young adults, likely due to screening. Most VZV testing appeared relevant to clinical management; however, inappropriate IgM testing was identified. Appropriate testing is important to guide clinical and public health management for varicella and herpes zoster.

INTRODUCTION: Testing for immunity to measles, mumps, and rubella should include only IgG; IgM testing is appropriate only if acute illness is suspected. The appropriateness of measles, mumps, and rubella IgM testing was evaluated in a national administrative dataset. METHODS: Laboratory testing for measles, mumps, and rubella during 2019-2022 was analyzed in 2024 using HealthVerity administrative claims and laboratory data. IgG, IgM, and reverse-transcriptase polymerase chain reaction (RT-PCR) testing are described by year, demographics, and region. IgM testing was examined for appropriateness, defined as an IgM test combined with diagnostic codes indicative of acute illness. RESULTS: During 2019-2022, IgM testing represented a small proportion of serologic testing (measles: 3.3%, mumps: 2.4%, rubella: 2.1%) but appeared to be appropriately performed in only 15.4% of cases for measles, 32.8% of cases for mumps, and 10.2% of cases for rubella. IgM testing was more commonly performed for female patients, with the largest discrepancy seen for rubella (90.5% female vs 9.5% male). IgM for measles and mumps was more often performed appropriately for persons aged 0-19 years (37.6% and 60.1%) compared with persons aged 20-49 years (11.8% and 22.0%) and 50+ years (16.5% and 33.8%). CONCLUSIONS: The majority of IgM testing for measles, mumps, and rubella during this period appeared inappropriate. Clinicians and health systems could ensure that IgG testing alone is performed when evaluating for immunity through modifications to electronic medical records and commercial laboratories could ensure that providers are able to test for IgG alone when evaluating immunity.

Small sample sizes have limited prior studies' ability to capture severe COVID-19 outcomes, especially among Ad26.COV2.S vaccine recipients. This study of 18.9 million adults aged ≥18 years assessed relative vaccine effectiveness (rVE) in three recipient cohorts: (1) primary Ad26.COV2.S vaccine and Ad26.COV2.S booster (two Ad26.COV2.S), (2) primary Ad26.COV2.S vaccine and mRNA booster (Ad26.COV2.S+mRNA), (3) two doses of primary mRNA vaccine and mRNA booster (three mRNA). The study analyzed two de-identified datasets linked using privacy-preserving record linkage (PPRL): medical and pharmacy insurance claims and COVID-19 vaccination data from retail pharmacies. It assessed the presence of COVID-19 during January 1-March 31, 2022 in: (1) any claim, (2) outpatient claim, (3) emergency department (ED) claim, (4) inpatient claim, and (5) inpatient claim with intensive care unit (ICU) admission. rVE for each outcome comparing three recipient cohorts (reference: two Ad26.COV2.S doses) was estimated from adjusted Cox proportional hazards models. Compared with two Ad26.COV2.S doses, Ad26.COV2.S+mRNA and three mRNA doses were more effective against all COVID-19 outcomes, including 57% (95% CI: 52-62) and 62% (95% CI: 58-65) rVE against an ED visit; 44% (95% CI: 34-52) and 54% (95% CI: 48-59) rVE against hospitalization; and 48% (95% CI: 22-66) and 66% (95% CI: 53-75) rVE against ICU admission, respectively. This study demonstrated that Ad26.COV2.S + mRNA doses were as good as three doses of mRNA, and better than two doses of Ad26.COV2.S. Vaccination continues to be an important preventive measure for reducing the public health impact of COVID-19.