Virology
Core concepts
Focus on three linked themes: specimen adequacy, detection method, and interpretation of serology. Respiratory and lesion samples go into viral transport medium and are kept cold, never frozen if culture is planned; blood for CMV antigenemia or viral load requires EDTA, and plasma for HIV RNA must be separated promptly. Cell culture and shell vial centrifugation detect cytopathic effect, but molecular amplification has largely replaced them for HSV, enterovirus, and respiratory viruses because of speed and sensitivity. Antigen tests are rapid but less sensitive than nucleic acid tests, so a negative rapid influenza result does not exclude infection.
Know the serologic patterns cold. Hepatitis B: HBsAg indicates current infection; anti-HBs indicates immunity; anti-HBc IgM indicates recent or acute infection; HBeAg indicates high infectivity. HIV screening uses a fourth-generation antigen/antibody assay, with differentiation and nucleic acid testing for confirmation. EBV uses heterophile antibody in older children and adults, but heterophile-negative cases need VCA IgM. Rubella and toxoplasma IgM must be interpreted cautiously because IgM can persist for months.
Traps
- Interpreting a positive IgM as acute infection without considering persistence or cross-reactivity.
- Calling a patient immune based on anti-HBs when the antibody came from passive transfusion of immunoglobulin.
- Ordering serology during the window period, when antigen or RNA testing is required.
- Assuming a negative rapid antigen test rules out influenza or RSV.
Rule of thumb
HBsAg negative, total anti-HBc positive, anti-HBs positive means resolved past infection. Isolated anti-HBc positivity suggests a window period, remote infection with waning anti-HBs, or a false positive, so follow with IgM and HBV DNA.