Coronavirus%20disease%202019%20(covid-19) Diagnosis

• Diagnostic testing involves detecting the virus itself (viral RNA or antigen) or detection of the antibodies or other biomarkers
• SARS-CoV-2 virus is detectable in the upper respiratory tract at 1-3 days before the onset of symptoms 
  • Concentration of the virus in the upper respiratory tract is highest around the time of onset of symptoms and then gradually declines
• The presence of viral RNA in the lower respiratory tract, and for a subset of individuals in the feces, increases during the second week of illness
• SARS-CoV-2 can be detected in a wide range of other body fluids and compartments, but is most frequently detected in respiratory material and, therefore, respiratory samples remain the specimen of choice for diagnostics

Nucleic Acid Amplification Test (NAAT) including Real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) Assay

• Recommended or gold standard confirmatory test of COVID-19 that detects viral RNA
• Nasopharyngeal specimen is preferred but alternatives can be oropharyngeal or saliva specimens 
• Used for diagnosis of current infection and not used to monitor response to treatment
• In ideal settings, it has high analytic sensitivity and specificity

Rapid Tests Based on Antigen Production 

• A lateral flow immunofluorescent sandwich assay intended for the qualitative detection of the nucleocapsid protein antigen from SARS-CoV-2 in nasopharyngeal and nasal swab specimens directly or after the swabs have been added to either the universal transport media or viral transport media
• Detects the presence of antigens expressed by the COVID-19 virus
• If the target antigen is present in sufficient concentrations in the sample, it will bind to specific antibodies fixed to a paper strip enclosed in a plastic casing and generate a visually detectable signal, typically within 30 minutes
• Antigen(s) detected are expressed only when the virus is actively replicating; therefore, such tests are best used to identify acute or early infection
• Can be used as an alternative to RT-PCR assay for the diagnosis of COVID-19 among symptomatic patients during the first week of illness
• Negative results should be confirmed with an RT-PCR test before having treatment decisions to prevent undue transmission

Rapid Antibody Tests

• Used for diagnosis of prior infection or infection of at least 3-4 weeks' duration
• Point of care and laboratory-based antibody immunoassays 
• Not recommended as a sole test for diagnosis of COVID-19
• Not recommended for mass testing and clearance for work of asymptomatic individuals because of its low sensitivity and high false-negative rates

Other Diagnostic Tests

• Complete blood count (CBC)
• Metabolic panel: Creatinine, liver function tests (LFTs), sodium, potassium, magnesium, calcium, albumin
• Inflammatory markers: Lactate dehydrogenase (LDH), ferritin, C-reactive protein (CRP), and procalcitonin
• Prothrombin and D-dimer
• Arterial blood gas (ABG) measurement
• Blood cultures if concomitant bacterial infection is suspected
• Respiratory tract specimen for influenza testing if prevalent
• Sputum, endotracheal aspirate (ETA), or bronchoalveolar lavage fluid culture and sensitivity
• Chest X-ray
• High-resolution plain chest computed tomography (CT) scan or CT pulmonary angiography (CTPA) 
• Electrocardiogram (ECG)

Mild to Moderate COVID-19 Disease (Non-severe COVID-19 or Clinical Stage 1-3)

• Mild disease is characterized by the absence of pneumonia or hypoxia and abnormal chest imaging findings
  • Presence of acute onset of fever or cough with any ≥3 of the following: Fever, cough, coryza, sore throat, diarrhea, anorexia/nausea/vomiting, loss of sense of smell or taste, general weakness/body malaise/fatigue, headache, myalgia
• Moderate disease features evidence of lower respiratory disease clinically or in imaging with saturation of oxygen (SpO₂) ≥94% on room air at sea level, and respiratory rate (RR) <30 breaths/minute

Severe COVID-19 Disease (Clinical Stage 4)

• Patients with severe disease exhibit severe pneumonia clinically and in diagnostic exams
  • Dyspnea, hypoxia and/or >50% lung involvement on imaging are present 
  • Oxygen saturation <90% on room air
• Patients with signs of severe respiratory distress
  • Adult: Use of accessory muscle, unable to complete full sentences, RR >30 breaths/minute
  • Children: Very severe chest wall in-drawing, grunting, central cyanosis, unable to breastfeed or drink, lethargy, convulsions or reduced level of consciousness

• Patients with pneumonia and impending respiratory failure that requires high-flow oxygen, non-invasive or invasive ventilation, acute respiratory distress syndrome (ARDS), sepsis or shock, deteriorating sensorium, or multi-organ failure