Rapid and quantitative detection of COVID-19 markers in micro-liter sized samples

Xiaotian Tan; Cory Lin; Jie Zhang; Maung Kyaw Khaing Oo; Xudong Fan

The disease (COVID-19) related to novel coronavirus (SARS-CoV-2) has caused tens of thousands of deaths and is becoming a severe threat to global health. However, diagnosis and prognosis of COVID-19 are still facing serious challenges. The current "gold standard" method to diagnose SARS-CoV-2 infection is based on the detection of viral RNA (N gene) in nasal swab samples with RT-PCR. However, PCR-based diagnosis is prone to false negatives due to the uncertainties in sample collection and the molecular mechanism of the test and is unable to track the immune response to the viral infection 1 . Earlier SARS-CoV related research 2, 3 and most recent studies on SARS-CoV-2 4, 5 have shown that SARS-specific antibodies, such as IgG, IgM, and IgA, can be detected in serum as early as seven days after viral infection (3-5 days after the symptoms appear) and can last for several years after recovery 1 . Similar immune response should also occur after a successful vaccination (>7 days after vaccination) 2, 3, 6 . Therefore, virus-specific antibodies in serum and secretory mucus (e.g., saliva and sputum) can be used as diagnostic markers for viral infection and for the evaluation of patient's adaptive immune responses (either from virus infection or from vaccination). As such, SARS-CoV-2-specific antibodies are currently listed among the diagnostic markers in the "COVID-19 Diagnosis and Treatment Plan (Provisional 7 th Edition)" published in China. In addition to SARS-CoV-2 specific antibodies, the viral antigen (such as the spike protein or S protein) in circulating blood can be used for the prognosis of COVID-19-related viremia 1, 7 . As one of the most commonly used targets for vaccine development, the serum concentration of the S protein is also a potential marker for early-stage vaccine responses, especially for sub-unit vaccines 8 .