Human coronaviruses comprise endemic HCoVs (229E, NL63, OC43, HKU1) that usually cause mild respiratory illness and zoonotic coronaviruses including SARS, MERS, and SARS‑CoV‑2 (the cause of COVID‑19); COVID‑19 caused a global pandemic with substantial morbidity and mortality and a clinical spectrum from asymptomatic to critical illness (including ARDS and multiorgan failure).
Diagnostic modalities include nucleic acid amplification tests (NAATs, e.g., RT‑PCR and rapid molecular assays) for acute infection detection, antigen detection tests (including point‑of‑care Ag‑RDTs) that detect viral proteins and are most useful early in symptomatic illness, and host serologic (antibody) tests (binding and neutralizing) that detect host immune response and are not for diagnosing acute infection.
Viral dynamics peak around symptom onset with upper respiratory viral load declining over ~10 days (but RNA may shed longer); thus NAATs are preferred for diagnosing current infection, antigen tests perform best within ~5–7 days of symptoms and should be used where WHO performance thresholds are met, and serology typically becomes reliable >14 days after symptom onset (IgM/IgA rise earlier but are less reliable; IgG seroconversion averages around 14 days).
Test performance varies by method and timing: NAATs generally have low limits of detection and high sensitivity, multiplex panels and platform‑specific assays (e.g., BioFire, ePlex, QIAstat) have defined LoDs and target lists, Ag‑RDT sensitivities are lower and variable (example studies report sensitivities from ~30% to >80% depending on the assay and timing), and serologic assay sensitivities improve ≥14–21 days PSO with ELISA/CLIA outperforming LFIA in pooled analyses.
Clinical contexts where serology is useful include supporting diagnoses of multisystem inflammatory syndrome in children (MIS‑C) and adults (MIS‑A) and evaluating post‑acute sequelae of SARS‑CoV‑2 infection (PASC)/long COVID; guidelines recommend combining antibody and viral testing for MIS‑C/MIS‑A evaluation and note serology may detect prior infection when NAAT is negative or unavailable.
Guidance from major authorities (CDC, WHO, NIH, IDSA, AAP, ACR) informs specimen selection (upper respiratory samples, saliva, breath in qualified settings, lower respiratory specimens when indicated), testing timing (test exposed contacts ≥5 days post exposure or immediately if symptomatic), isolation strategies, and limitations of serology (should not be used to determine immunity or return‑to‑work) and of antigen tests (negative results are presumptive and may need confirmation by NAAT).