What is the recommended diagnostic and treatment approach for a patient suspected of having a COVID-19 (Coronavirus Disease 2019) infection that can be diagnosed using Polymerase Chain Reaction (PCR)?

Diagnostic and Treatment Approach for COVID-19 Infection

RT-PCR testing is the gold standard for diagnosing COVID-19 infection, and should be performed as the first-line diagnostic test for all patients suspected of having COVID-19. 1, 2

Diagnostic Testing Algorithm

Initial Diagnostic Testing

• First-line test: RT-PCR on respiratory specimens

  • Preferred specimen types (in order of preference) 2:
    1. Nasopharyngeal (NP) swab
    2. Mid-turbinate (MT) swab
    3. Combined anterior nasal (AN) plus oropharyngeal (OP) swab
    4. Saliva or mouth gargle specimens

• Timing considerations:

  • Optimal testing time is 3 days after symptom onset (minimizes false-negative rate to 20%) 2
  • False-negative rates are highest during early infection (up to 100% on day 1,68% on day 4) 2

Confirmatory Testing

• A positive RT-PCR from any anatomical source should be considered confirmatory for SARS-CoV-2 infection 3
• For patients with high clinical suspicion but negative initial RT-PCR:
  • Collect and test lower respiratory tract specimens 3
  • Repeat testing is recommended as a single negative test does not rule out infection 4
  • Consider collecting multiple specimens over multiple days 1, 4

Alternative Testing Options

• Point-of-care antigen tests:
  • May be used as an alternative to RT-PCR when RT-PCR is unavailable 3
  • Lower sensitivity than RT-PCR, especially in asymptomatic individuals 2
  • Positive results have high specificity and can guide treatment decisions 2

Radiological Assessment

• Chest imaging should be performed to assess disease severity and detect complications:

  • Chest CT scan is the most accurate radiological tool for COVID-19 diagnosis 1
  • Chest X-ray (CXR) can be used when CT is unavailable 1
  • Lung ultrasound may be used where standard thoracic imaging is limited 3

• Important caveat: A normal chest CT scan cannot exclude COVID-19 diagnosis, especially in patients with early symptoms or asymptomatic patients 1

Laboratory Testing for Disease Severity Assessment

Recommended Laboratory Tests

1. Complete blood count with differential 2, 3

   • White blood cell count
   • Absolute lymphocyte count
   • Absolute neutrophil count
   • Neutrophil-to-lymphocyte ratio
   • Platelet count
   • Hemoglobin

2. Inflammatory markers 2, 3

   • C-reactive protein (CRP)
   • Ferritin
   • Procalcitonin
   • Erythrocyte sedimentation rate (ESR)
   • Interleukin-6 (if available)

3. Coagulation studies 2, 3

   • D-dimer
   • Fibrinogen
   • Prothrombin time (PT)
   • Activated partial thromboplastin time (aPTT)

4. Other biochemical tests 3

   • Creatinine
   • Liver function tests
   • Lactate dehydrogenase
   • Troponin (especially with cardiopulmonary symptoms)

Treatment Approach

Mild to Moderate Disease (Outpatient)

• Supportive care
• Symptom management
• Monitor for disease progression
• Consider antiviral therapy based on risk factors and timing from symptom onset

Severe Disease (Requiring Hospitalization)

1. Respiratory support as needed:

   • Supplemental oxygen
   • High-flow nasal cannula
   • Non-invasive ventilation
   • Mechanical ventilation for respiratory failure

2. Antiviral therapy:

   • Remdesivir should only be administered in settings with immediate access to medications for treating severe reactions 2

3. Immunomodulatory therapy:

   • Corticosteroids for patients requiring oxygen
   • Consider IL-6 inhibitors in selected patients

4. Management of co-infections:

   • Do not routinely administer antibiotics for COVID-19 patients 1
   • Consider empiric antibiotics only when bacterial co-infection is suspected based on clinical, laboratory, and imaging findings 1
   • If bacterial co-infection is suspected in non-critically ill patients, use antibiotics that cover both typical and atypical pathogens 1

Special Considerations for Surgical Patients

• If RT-PCR testing is unavailable for a surgical patient, the patient should be managed as if COVID-19 positive 1
• Use all protective measures and dedicated pathways for operating rooms 1
• For stable patients where COVID-19 cannot be ruled out, consider transfer to a COVID-19 hub hospital if available 1

Pitfalls and Caveats

1. False-negative RT-PCR results can occur due to:

   • Improper specimen collection 5
   • Testing too early in the course of infection 2, 5
   • Low viral loads 5
   • Technical issues with the testing kit 5

2. Do not rely solely on radiological findings to exclude COVID-19 1

3. Do not use serum biomarkers alone to decide when to start antimicrobials 1

4. Do not routinely repeat testing to determine the end of isolation period 2

5. Avoid unnecessary testing in asymptomatic or mildly symptomatic outpatients 2