Differentiating COVID-19 from other causes of viral pneumonia, like herpes simplex (HSV), can be complicated by shared clinical and laboratory features. Viral pneumonia is mostly diagnosed based on molecular or serological techniques. Serological immunoassay interferences, often attributed to concurrent appearance of heterologous (viral) immunoglobulins, is well-known, but has not been studied in COVID-19 patients. Following false positive HSV IgM results in our index patient, twenty-five other SARS-CoV-2 patients were tested for HSV-1/2 IgM with the chemiluminescent Liaison® assay and Euroimmun® ELISA. 45 % of COVID-19 patients tested positive for HSV IgM with Liaison®. No HSV indices were positive with Euroimmun® ELISA, suggesting immunoassay interference. Significant correlation between HSV IgM and SARS-CoV-2 IgM/IgG positivity was found. Adding 0.5% polyvinylpyrrolidone (PVP), inhibiting non-specific solid-phase adsorption, abolished interference in 22% of false positive cases, suggesting interference caused by solid-phase reactive IgM. Hence, serologic immunoassay results should be interpreted with caution in COVID-19 patients.
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