## Diagnostic Approach to COVID-19 **Key Point:** RT-PCR (reverse transcription polymerase chain reaction) from nasopharyngeal or oropharyngeal swab is the gold standard and most appropriate initial confirmatory test for acute SARS-CoV-2 infection. ### Why RT-PCR is the Best Choice **High-Yield:** RT-PCR detects viral RNA directly and is: - Most sensitive (95–98%) and specific (>99%) during the acute phase (first 5–7 days) - Becomes positive within 1–3 days of symptom onset - Remains positive for 2–3 weeks in respiratory secretions - The reference standard endorsed by WHO, CDC, and ICMR guidelines ### Timing and Specimen Type | Phase | Best Specimen | Test of Choice | |-------|---------------|----------------| | Acute (0–7 days) | Nasopharyngeal/oropharyngeal swab | RT-PCR | | Early (5–14 days) | Lower respiratory tract (sputum, BAL) | RT-PCR | | Late (>14 days) | Serum | IgG antibodies | **Clinical Pearl:** Nasopharyngeal swab has higher sensitivity than oropharyngeal swab alone; combined swabs are preferred. Saliva and sputum samples are also acceptable alternatives. ### Why Other Investigations Are Not First-Line **Warning:** Serum antibodies (IgM/IgG) take 7–14 days to appear and are not useful for acute diagnosis in the first week—they are better for seroepidemiological surveys and determining past infection. Chest CT, while sensitive for pneumonia, is not a confirmatory test for the virus itself—it shows morphology but not etiology. Viral culture is slow, requires BSL-3 facilities, and is not practical for routine diagnosis. ### Specimen Collection Timing **Tip:** If the first RT-PCR is negative but clinical suspicion remains high (e.g., typical CT findings), repeat RT-PCR 24–48 hours later, as early sampling may yield false negatives. [cite:Harrison 21e Ch 197]
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