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Serology Coronavirus Tests Can Complement PCR Methods, ID Asymptomatic Infections, Study Says

NEW YORK – A team of researchers in Chongqing, China conducted a study of antibody responses to the SARS-CoV-2 virus in patients with COVID-19, and found that 100 percent of the patients tested positive for antiviral immunoglobulin-G (IgG) 19 days after the onset of symptoms.

As they reported in Nature Medicine on Wednesday, the researchers studied serological samples from 285 COVID-19 patients. They found that seroconversion for IgG and immunoglobulin-M (IgM) occurred simultaneously or sequentially in these patients, and that both IgG and IgM titers plateaued within six days of seroconversion.

"Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections," the authors wrote.

Antibody testing for SARS-CoV-2 is being used in New York and California to estimate the scope of virus's spread. Such testing has proven reliable in previous coronavirus epidemics — studies on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) showed that virus-specific antibodies were detectable in 80 percent to 100 percent of patients at two weeks after the onset of symptoms, the researchers said. But the antibody response against SARS-CoV-2 remain poorly understood and the clinical utility of serological testing is unclear.

Indeed, the current antibody testing efforts have returned a wide variety of results — the New York State survey found a 21.2 percent positive rate for New York City residents, while a survey of 3,330 people in Santa Clara County, California, estimated a population prevalence of between 2.5 percent and 4.2 percent.

For their study, the researchers enrolled 285 patients with COVID-19 from three designated hospitals, 70 of whom had sequential samples available. They used a magnetic chemiluminescence enzyme immunoassay (MCLIA) to detect virus-specific antibodies in the samples and found that 100 percent of patients were positive for virus-specific IgG approximately 17 to 19 days after symptom onset. They also observed that the proportion of patients with positive virus-specific IgM reached a peak of 94.1 percent approximately 20 to 22 days after symptom onset.

During the first three weeks after symptom onset, there were increases in virus-specific IgG and IgM antibody titers, but IgM showed a slight decrease in the group who had virus-specific antibodies more than three weeks after symptom onset compared to the group who had such antibodies three weeks or less after symptom onset, the researchers said. IgG and IgM titers in the severe group were higher than those in the non-severe group, although they only observed a significant difference in IgG titer in the two-week post-symptom onset group.

The researchers also analyzed whether the criteria for confirmation of MERS-CoV infection recommended by the World Health Organization — including seroconversion or a fourfold increase in IgG-specific antibody titers — could be suitable for the diagnosis of COVID-19. They collected an initial sample from 41 patients in the first week of illness and a second two to three weeks later. Of the patients whose IgG was initially seronegative in the first week of illness, 51.2 percent underwent seroconversion. A total of 18 patients were initially seropositive in the first week of illness; of these, eight patients had a fourfold increase in virus-specific IgG titers. Overall, the researchers found, 70.7 percent of the patients with COVID-19 met the criteria of IgG seroconversion and/or fourfold increase or greater in the IgG titers.

To investigate whether serology testing could help identify patients with COVID-19, they screened 52 suspected cases in patients who displayed symptoms of COVID-19 or abnormal radiological findings and for whom testing for viral RNA was negative in at least two sequential samples. Of the 52 suspected cases, four had virus-specific IgG or IgM in the initial samples.

They further demonstrated the application of serology testing in surveillance in a cluster of 164 close contacts of patients with known COVID-19. Sixteen individuals were confirmed to be infected with SARS-CoV-2 by RT-PCR, with three cases reporting no symptoms. The other 148 individuals had negative RT-PCR results and no symptoms. The team collected serum samples from these 164 individuals for antibody tests about 30 days after exposure and found that the 16 RT-PCR-confirmed cases were all positive for virus-specific IgG and/or IgM. Further, seven of the 148 individuals with negative RT-PCR results had positive virus-specific IgG and/or IgM, indicating that 4.3 percent of the close contacts were missed by the nucleic acid test.

"Our study showed that the criteria for the confirmation of MERS-CoV infection are suitable for most patients with COVID-19. However, a collection of the first serum sample as early as possible is required for some patients to meet these criteria," the authors concluded. "Our data indicate that virus-specific antibody detection for COVID-19 could be important as a complement to nucleic acid testing for the diagnosis of suspected cases with negative RT-PCR results and in surveying for asymptomatic infection in close contacts. Confirming suspected COVID-19 cases as early as possible with the help of serological testing could reduce exposure risk during repeated sampling and save valuable RT-PCR tests."