Adult Invasive Enterovirus Infections Clustered in Younger Patients and the Immunocompromised in Alberta
A population-based surveillance study from Alberta found that invasive enterovirus and parechovirus infections in adults were uncommon overall, but they did not fall evenly across the population. The burden clustered in younger adults and in patients whose immune systems were already weakened, a pattern that fits the biology of picornaviruses: these infections are usually contained by intact host defenses, but they can spread beyond the usual mucosal sites when antibody-mediated control is impaired.
The investigators reviewed adult testing from May 2023 through December 2025 and identified 15,621 samples submitted for enterovirus and parechovirus testing. Only 162 samples were positive, a rate of 1.0%, and 51 of those positives met the study definition of invasive infection. Most invasive detections came from cerebrospinal fluid, with fewer from blood and cardiac tissue. One parechovirus-positive invasive case was found; the remainder were enteroviruses.
Cerebrospinal Fluid Drove Most Diagnoses, and Meningitis Dominated the Presentation
Clinical presentation leaned heavily toward the central nervous system. Among 39 patients with invasive infection, the median age was 32.5 years, with a range from 17 to 72 years. Slightly more than half were female. Most patients lived in urban areas, though the study also captured a smaller rural subgroup, reinforcing that the surveillance system was drawing from a broad provincial population rather than a single referral center.
Aseptic meningitis accounted for 31 cases, or 79.5% of patients. Encephalitis or meningoencephalitis was less common, appearing in six patients. Two patients died, and only two required critical care admission. Most patients were hospitalized, but the median length of stay was just three days, consistent with the generally self-limited course that enterovirus meningitis can follow in immunocompetent hosts. The picture changes quickly when host immunity is compromised.
CSF testing was performed in 37 patients, and every patient with aseptic meningitis had CSF leukocytosis above 5 × 10^6 leukocytes/L. Among the 30 patients who underwent CNS imaging, 28 had no acute abnormality reported. In practice, that combination matters: a normal scan does not exclude invasive viral disease, and CSF remains the key diagnostic specimen when neurologic symptoms raise concern for enterovirus infection.
Younger Age Carried the Highest Incidence, Not Older Age
The incidence rate for invasive enterovirus and parechovirus infection was 0.37 cases per 100,000 person-years. Rates were higher in patients younger than 50 years than in those 50 years and older, with an incidence rate ratio of 8.2 and a p value below 0.001. The age gradient is striking because it runs against the usual expectation that infections with the worst outcomes always concentrate in older adults. Here, the explanation appears to lie less in age itself than in exposure patterns, diagnostic intensity, and the concentration of specific risk states in younger adults, especially those receiving immune-modifying therapy.
Annual incidence ranged from 0.20 to 0.56 cases per 100,000 person-years. Rates appeared higher in 2025 than in 2024, with an incidence rate ratio of 2.1, although the p value of 0.11 keeps that observation from crossing conventional statistical thresholds. The seasonal curve also suggested temporal clustering, a familiar feature of enterovirus circulation, which often rises in waves rather than through a flat year-round pattern.
Ocrelizumab-Associated Cases Point to B-Cell Depletion as a High-Risk State
Two patients developed severe disseminated enterovirus infection while receiving ocrelizumab. This is the most clinically important safety signal in the cohort. B-cell depletion can blunt neutralizing antibody production, leaving patients less able to contain enteroviruses after systemic spread. In patients with hypogammaglobulinemia or other immune deficits, that biologic vulnerability can translate into persistent viremia, multisystem disease, or a sepsis-like syndrome rather than the usual self-limited meningitis.
The Alberta cohort fits that mechanism. Immunocompromise was a recognized risk factor throughout the study period, and the severe cases in ocrelizumab-treated patients echo prior reports of disseminated enterovirus disease in people with B-cell depletion. The clinical problem is not abstract: neurologic symptoms, shock-like illness, or unexplained systemic inflammation in this setting should trigger a low threshold for enterovirus testing, especially when CSF, blood, or tissue samples can provide direct molecular confirmation.
A single positive result can change the entire diagnostic frame.
Rare Disease, Real Surveillance Burden
Even with a low overall incidence, the study shows why laboratory surveillance remains essential. Enteroviruses and parechoviruses are globally circulating viruses that usually cause mild or unapparent infection, but their ability to invade the central nervous system or disseminate in immunocompromised hosts gives them disproportionate clinical weight. The cohort also demonstrates how much case finding depends on the quality and reach of PCR-based testing. Alberta used a centralized multiplex real-time reverse transcription PCR assay across a wide range of specimen types, and invasive cases were defined strictly by detection in sterile-site material such as blood, CSF, joint fluid, or tissue biopsy.
That laboratory framework matters for public health tracking and for bedside decision-making. If testing is limited to respiratory or mucosal specimens, true invasive disease can be missed, especially when presentation is dominated by neurologic symptoms or when the patient has already progressed beyond the initial exposure window. Genotyping of invasive enterovirus isolates also adds epidemiologic value by clarifying which viral lineages are circulating in severe disease, even though this article does not provide a complete genotype breakdown in the main text.
Detection Gaps Remain a Practical Problem
The authors close on a straightforward public health message: continuous surveillance and ongoing optimization of enterovirus and parechovirus detection assays are needed. The study period was relatively short, the number of invasive cases was small, and the statistical precision around year-to-year variation was limited. Those constraints do not weaken the central clinical signal. Adult invasive enterovirus disease is rare in Alberta, but when it appears, it concentrates in younger adults and in patients with impaired immune function, including those treated with ocrelizumab.
The bedside implication is direct. In adults with meningitis, encephalitis, myocarditis, or unexplained systemic illness, enterovirus should remain on the differential diagnosis even outside pediatric practice. In patients receiving B-cell depleting therapy, that suspicion should rise further, because the consequences of delayed recognition can be severe and the usual reassuring assumptions about viral self-limitation no longer hold.