Antibodies responding to covid-19 coronavirus, illustration
Illustration of antibodies (red and blue) responding to an infection with the new coronavirus SARS-CoV-2 (purple). The virus emerged in Wuhan, China, in December 2019, and causes a mild respiratory illness (covid-19) that can develop into pneumonia and be fatal in some cases. The coronaviruses take their name from their crown (corona) of surface proteins, which are used to attach and penetrate their host cells. Once inside the cells, the particles use the cells' machinery to make more copies of the virus. Antibodies bind to specific antigens, for instance viral proteins, marking them for destruction by other immune cells.

A prior infection with SARS-CoV-2, the virus that causes COVID-19, appears to be protective against reinfection for at least a few months, according to a new study from the National Cancer Institute (NCI). This finding may explain why reinfection is relatively rare, and it could have implications on decisions about returning to work after infection, school attendance, and the prioritization of vaccine distribution.

The study was launched to better understand whether, and to what degree, detectable antibodies against SARS-CoV-2 protect people from reinfection. SARS-CoV-2 is a new type of coronavirus, and the question of immunity is still not determined. The CDC says that reported cases of COVID-19 reinfection “remain rare.” According to a British Medical Journal (BMJ) report, “Worldwide, 31 confirmed cases of COVID-19 reinfection have been recorded, although that could be an underestimate from delays in reporting and resource pressures in the ongoing pandemic.” (BMJ, Jan. 2021)

For this study, researchers at NCI collaborated with two health care data analytics companies (HealthVerity and Aetion, Inc.) and five commercial laboratories, Including Quest Diagnostics and Labcorp. The findings were published on today in JAMA Internal Medicine. http://dx.doi.org/10.1001/jamainternmed.2021.0366 

“The data from this study suggest that people who have a positive result from a commercial antibody test appear to have substantial immunity to SARS-CoV-2, which means they may be at lower risk for future infection,” said the study’s leader, Lynne Penberth, M.D., MPH, and associate director of NCI’s Surveillance Research Program. “Additional research is needed to understand how long this protection lasts, who may have limited protection, and how patient characteristics, such as comorbid conditions, may impact protection. We are nevertheless encouraged by this early finding.”

For this study, NCI researchers and their collaborators aggregated and analyzed patient information collected from multiple sources, including commercial labs, electronic medical records, and private insurers.

The researchers ultimately obtained antibody test results for more than 3 million people who had a SARS-CoV-2 antibody test between Jan. 1 and Aug. 23, 2020. This represented more than 50% of the commercial SARS-CoV-2 antibody tests conducted in the U.S. during that time. Nearly 12% of these tests were antibody positive; most of the remaining tests were negative, and less than 1% were inconclusive.

About 11% of the seropositive individuals and 9.5% of the seronegative individuals later received a nucleic acid amplification test (NAAT)–sometimes referred to as a PCR test–for SARS-CoV-2. The research team looked at what fraction of individuals in each group subsequently had a positive NAAT result, which may indicate a new infection. The study team reviewed NAAT results at several intervals: 0-30 days, 31-60 days, 61-90 days, and >90 days because some people who have recovered from a SARS-CoV-2 infection can still shed viral material (RNA) for up to three months (although they likely do not remain infectious during that entire period).

The team found that, during each interval, between 3% and 4% of the seronegative individuals had a positive NAAT test. But among those who had originally been seropositive, the NAAT test positivity rate declined over time. When the researchers looked at test results 90 or more days after the initial antibody test, only about 0.3% of those who had been seropositive had a positive NAAT result–about one-tenth the rate in those who had been seronegative.

Although these results support the idea that having antibodies against SARS-CoV-2 is associated with protection from future infection, the authors note important limitations to this study. In particular, the findings come from a scientific interpretation of real-world data, which are subject to biases that may be better controlled for in a clinical trial. For example, it is not known why people who had tested antibody positive went on to have a PCR test. In addition, the duration of protection is unknown; studies with longer follow-up time are needed to determine if protection wanes over time.

To continue to address this question, NCI is supporting clinical studies that monitor infection rates in large populations of people whose antibody status is known. These are known as “seroprotection” studies. NCI is also sponsoring ongoing studies using real-world data to assess the longer-term effect of antibody positivity on subsequent infection rates.

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