Deciphering Positive Cytomegalovirus Immunoglobulin M Test Results in Immunocompetent Adults Hospitalized With Illness Suspicious for Acute Cytomegalovirus Infection: A Multihospital Study.

BACKGROUND: Previously healthy adults hospitalized with an acute undifferentiated illness who test positive for cytomegalovirus (CMV) immunoglobulin M (IgM) in their serum may have a primary CMV infection, CMV reactivation/reinfection, or a false-positive result. We aimed to understand how clinicians interpret and incorporate positive CMV IgM test results into their diagnostic and management decisions.

METHODS: This was a retrospective case series study of 13 previously healthy, immunocompetent adults hospitalized with an acute illness in a 12-hospital system from 1 January 2017 to 1 January 2020, who tested positive for CMV IgM within 3 days of hospitalization. Twelve of 13 had CMV immunoglobulin G (IgG).

RESULTS: Among these 13 adults (median age, 36 years), elevated liver enzymes (100%), fever (85%), hepatosplenomegaly (54%), and headache (38%) were common. Lymphocytosis was observed in 5 patients, reactive lymphocytes in 3, and 1 patient died from hemophagocytic lymphohistiocytosis. Dual positivity for CMV and Epstein-Barr virus (EBV) IgM was frequent, yet only 1 patient was tested for both CMV and EBV DNA in blood or for CMV IgG avidity index, which indicated a primary CMV infection. Of the 6 patients with CMV DNA in blood, 4 received anti-CMV treatment. Uncertainty regarding CMV's role in the illness was common, and final assessments varied even among cases with similar clinical presentations and serologic patterns.

CONCLUSIONS: Interpreting positive CMV IgM results in immunocompetent adults hospitalized with acute illness is challenging and ambiguous due to test limitations and confounders. Supplemental CMV IgG avidity testing can help determine whether primary CMV infection caused the illness, thereby refining the diagnosis and potentially influencing clinical decision-making.