Diagnostic Tests for COVID-19

In general, the diagnosis of COVID-19 in children is the same as that in adults, which is based on the clinical and epidemiological history of the patient. Clinicians should have a suspicion of COVID-19 when a child shows one or more clinical manifestations of COVID-19 and, within 14 days before the onset of the disease, had at least one of the risks of COVID-19, that is, living or history of traveling in areas with the local transmission of SARS-CoV-2 or history of close contact with a confirmed case of COVID-19. The diagnosis is supported by a chest X-ray or CT scan, and diagnostic tests to identify the virus or immune response to the virus. Because of the high morbidity and transmission rates of COVID-19, accurate and timely diagnostic tests are important to control the outbreak of the disease and to help the clinician in deciding on diagnosis and management. Currently, the diagnostic tests for COVID-19 mainly consist of molecular tests to identify the RNA of the virus and serological tests that detect the immunoglobulins against SARS-CoV-2. REAL-TIME REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION The gold standard of COVID-19 is the detection of the virus, SARS-CoV-2, on a variety of specimens, including naso/oropharyngeal swabs, sputum, bronchoalveolar lavage fluid, bronchoscope brush biopsies, or feces through nucleic acids amplification test using real-time reverse transcriptase polymerase chain reaction (rRT-PCR).[1] This test can detect the RNA at the early stage of infection when the viral load is low and antibodies have not been formed, as shown in [Figure 1].[2]Figure 1: Viral load and the clinical course during SARS-CoV-2 infection (taken from reference[2])If done properly, the diagnostic values of rRT-PCR are good. The high specificity of rRT-PCR indicates a low probability of false-positive. Nevertheless, the false-negative of this test was reported as high as 41%.[3,4,5] Several studies have identified that the false-negative can occur if the amount of virus in the specimen is too low to be amplified and detected, which relates to sampling operation, specimen source, sampling timing (before or after symptoms onset), and the performance of detection kit.[2] A study from China reported that within 14 days of the onset of the disease, sputum samples had the highest yield of the virus (85% and 78%), followed by nasal swabs (73% and 63%) in severe and mild cases, respectively.[6] Further studies are needed to determine the most appropriate specimens and timing for peak viral load during SARS-CoV-2 infection. In a clinical setting, the decision to treat or not to treat a patient as COVID-19 should not rely on the result of rRT-PCR only because a negative result does not completely rule out the possibility of COVID-19.[7] Re-testing should be considered in a patient with high suspicion of COVID-19. SEROLOGICAL TESTS Serological tests for COVID-19 measure antibodies in the blood when the body is infected with SARS-CoV-2. There are two assay methods of serological tests available: automated tests (enzyme-linked immunosorbent assays [ELISA] or chemiluminescence enzyme immunoassays [CLIA]) and rapid detection test (lateral flow immunoassays [LFIA]). The antibodies remain in the blood for several weeks to months after symptom onset; therefore, the test can identify recent or previous exposure to the virus, depending on the type of the immunoglobulin detected. IgM antibodies against SARS-CoV-2 are detectable in the blood a few days after initial infection, but the presence of IgM throughout infection has not been well characterized. IgG is detectable as early as three days from the onset of the symptom or 7–10 days after the initial infection.[8] Although the serology tests are easier, faster, and cheaper to perform at the point of care than rRT-PCR, the diagnostic accuracies of these tests are also problematic. A recent systematic review of 40 studies documented that the pooled sensitivity of ELISA for IgG and IgM was 84.3% (95% confidence interval: 75.6%–90.9%), of LFIA was 66.0% (49.3%–79.3%), and of CLIA was 97.8% (46.2%–100%).[9] The pooled specificity ranged from 96.6% to 99.7%. This test will falsely identify 44% to 87% of persons as not having COVID-19 when the test was done within one week of symptom onset. In the later stage of the disease, the false-negative of IgG serology tests was also of concern. These results imply that the utility of the serological test in clinical decision-making, both establishing the diagnosis and initiation of the treatment, is very limited. The serological tests are beneficial for large-scale use to assess the seroprevalence in a population, not for establishing the diagnosis. HOW TO DIAGNOSE COVID-19 WHEN DIAGNOSTIC TESTS NOT READILY AVAILABLE Despite the limitation of the accuracy of the diagnostic tests for COVID-19, clinicians should perform rRT-PCR on all symptomatic children to confirm COVID-19. In fact, this test is not always available or cannot be accessed in some settings, so that a presumptive or probable diagnosis should be made. A simple algorithm or a scoring system consists of clinical findings, and simple laboratory investigations will be very valuable to help clinicians in this situation. Nevertheless, no studies or recommended guidelines have been published. High probability of COVID-19 is more likely in a symptomatic child with no other apparent causes of the symptoms. Moreover, if the child is from an area with a high prevalence of local transmission rate COVID-19, in this situation, it is reasonable to make a presumptive diagnosis of COVID-19. The decision of treatment will depend on the severity of the clinical manifestations, the presence of comorbid, and the balance between the risk and benefit of the treatment. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.