ACP Practice Points Reflect Current Uncertainty of Natural Immunity from COVID-19

The American College of Physicians’ (ACP) Scientific Medical Policy Committee (SMPC) recently published living practice points to help clinicians navigate the best use of SARS-CoV-2 antibody tests.

The Practice Points, published in the Annals of Internal Medicine, were based on a systematic evidence review of the antibody response to SARS-CoV-2 infection done by the Portland VA Research Foundation. The practice points will be updated as more evidence is gathered.

The practice points are:

• Do not use SARS-CoV-2 antibody tests for the diagnosis of SARS-CoV-2 infection.
• Antibody tests can be useful for the purpose of estimating community prevalence of SARS-CoV-2 infection.
• Current evidence is uncertain to predict presence, level or durability of natural immunity conferred by SARS-CoV-2 antibodies against reinfection after SARS-CoV-2 infection.

“The availability of COVID-19 antibody tests raises critical questions as to their use and how they are interpreted by clinicians and ultimately for advising patients,” ACP President Jacqueline W. Fincher, MD, MACP, said in a statement. “Once a patient has tested positive for SARS-CoV-2 infection, the questions remain as to whether or not they will be protected from reinfection, how long antibody protection lasts and to what level.”

Fincher recommended that patients, including those who have a history of SARS-CoV-2 infection, continue to practice safety measures of frequent hand washing, wearing masks and maintaining physical distance.

The evidence review sought to address several key questions, including the prevalence, level and durability of anti-SARS-CoV-2 antibodies among those who are infected or have recovered from infection with SARS-CoV-2; whether anti-SARS-CoV-2 antibodies confer natural immunity against reinfection; how long immunity lasts; and unintended consequences of antibody testing.

It included an initial search of evidence through Aug. 4 and updated through Dec. 15. It included dozens of studies involving 16525 adults with SARS-CoV-2 infection ranging from asymptomatic to critical.

The review found evidence of an immune response after infection based on detectable IgA antibodies in most patients (low certainty), IgM in most patients (moderate certainty), IgG in nearly all patients (moderate certainty) and neutralizing antibodies in nearly all patients (low certainty).

Antibody levels peak on average between 20 and 31 days after symptom onset or confirmed infection, and evidence suggests they persist over time, with neutralizing antibodies detected up to 152 days.

Presence and level of antibodies may vary by factors such as age, race, sex, race/ethnicity and presence and severity of symptoms. Therefore, antibody tests are not recommended to diagnose SARS-CoV-2 infection. The review also noted that cross-reactivity with other coronaviruses may result in false positivity. Substantial variation in sensitivity, specificity and accuracy among available antibody tests also may contribute to false results.

The review also found no evidence directly evaluating the association between antibodies and natural immunity and insufficient evidence about unintended consequences of antibody testing.

Ongoing surveillance of literature is planned through December 2021.

“These practice points shed important light on this emerging topic,” Fincher said. “However, significant evidence gaps remain and additional research and studies are needed to evaluate the protection these tests provide and to further understand how variability of patient demographics can impact results.”

A recent study found that rapid antibody testing can be effective at helping predict a prior COVID-19 infection.

Still, the accuracy of COVID-19 antibody tests varies. A recent review of studies found that antibody testing platforms have varying levels of accuracy and several limitations, including high or unclear risk of bias. Pooled sensitivity of tests measuring IgG or IgM was 84.3% (range from 75.6% to 90.9%) compared with 66% (range from 49.3% to 79.3%) for lateral flow assays and 97.8% (range from 46.2% to 100%) for chemiluminescent immunoassays.

Among the tests available, a new test developed by Vibrant American Clinical Labs, was granted Emergency Use Authorization by the US Food and Drug Administration. It tests for as many as a dozen viral antigens and can predict the severity of a patient’s symptoms.