Serologic Tests for SARS-CoV-2: First Steps on a Long Road

Three teams of investigators are developing serologic tests to answer key questions about SARS-CoV-2. Guo and colleagues looked at the kinetics of immunoglobulin M, (IgM), IgA, and IgG antibody response in infected patients using an enzyme-linked immunosorbent assay (ELISA) based on SARS-CoV-2 viral nucleocapsid protein. The researchers assessed 208 plasma samples from 82 confirmed and 58 probable COVID-19 cases.

Antibodies were found as early as 1 day after the onset of symptoms. IgM ELISA detected more cases than polymerase chain reaction (PCR) on day 5.5 of illness. The combination of IgM ELISA plus PCR detected 98.6% of cases versus 51.9% with a single PCR. During the first 5.5 days, PCR had higher positivity rate than IgM; the reverse was true after day 5.5. No cross reactivity was found with common coronaviruses that cause upper respiratory infections. In a family cluster, PCR-negative family contacts of COVID-19 cases had positive serologic assay, confirming the presence of antibodies in asymptomatic infection.

Zhao and colleagues assessed total antibody, IgM antibody, and IgG antibody against SARS-CoV-2 on serial blood samples collected from 173 patients (median age, 48 years) with PCR-confirmed COVID-19 in Shenzhen, China. Plasma samples were tested using ELISA kits supplied by Beijing Wantai Biological Pharmacy Enterprise Co., Ltd., Beijing, China.

In samples collected during the first 7 days after illness onset, positive rates were 66.7% for PCR and 38.3% for antibody assays. During the second week after illness onset, positive rates were 54.0% for PCR and 89.6% for antibody assays. The combined use of PCR and antibody testing improved identification of positivity through various phases of illness. Increases in antibody levels were not associated with RNA clearance, including in three patients with critical illness. A strong correlation was found between clinical severity and antibody titer more than 2 weeks after illness onset. Total antibody was more sensitive than IgM or IgG antibody.

Li and colleagues developed a lateral flow immunoassay that detects IgM and IgG antibodies simultaneously and can test finger-prick blood, serum, and plasma. The point-of-care test provides results within 15 minutes and requires no special equipment. The assay was tested in six provinces in China on blood samples from 397 PCR-confirmed COVID-19 patients and on 128 negative patients.

Overall sensitivity was 88.7%, and specificity was 90.6%. Several authors were affiliated with the company that developed the test (Jiangsu Medomics Medical Technology Co., Ltd., Nanjing, China).