ACP Releases Updated Practice Points on the Role of Natural Immunity in COVID-19

Father with surgical face mask, is putting a hand made protective face mask on his little daughter for the COVID-19 pandemic.
The American College of Physicians has released version 2 of their rapid, living practice points to summarize currently available evidence on the antibody response and natural immunity conferred by prior COVID-19 infection.

The American College of Physicians (ACP) recently released version 2 of their rapid, living practice points in which they summarize the current evidence on the antibody response in COVID-19 infection and its role in protecting against COVID-19 reinfection. These clinical practice points, published in Annals of Internal Medicine, were updated by the ACP’s Scientific Medical Policy Committee (SMPC).

Practice Point 1 (no change)

The SMPC reaffirmed their recommendation against the use of SARS-CoV-2 antibody tests in the diagnosis of COVID-19 infection. Although findings from prior studies have shown that patients infected with COVID-19 develop detectable antibodies, the SMPC noted several reasons for this recommendation:

  • There is evidence (low to moderate certainty) that variations may occur in the timing of peak antibody response and the duration in which antibodies remain detectable following initial COVID-19 infection.
  • Factors such as age, sex, and race/ethnicity (low certainty evidence), as well as the severity of initial infection (insufficient evidence), may also lead to variations the antibody response.
  • Evidence from 10 studies was insufficient to determine whether detectable antibody responses or the risk for false-negative and false-positive results vary by type of immunoassay.
  • Evidence from 13 studies was insufficient to determine whether patients with comorbidities have differing antibody responses to COVID-19 infection.

Practice Point 2 (updated rational)

The SMCP provided an updated rationale to reaffirm their recommendation against the use of SARS-CoV-2 antibody tests to predict the duration of natural immunity among previously infected patients, including natural immunity against SARS-CoV-2 variants. Despite the emergence of new evidence from recently published studies (n=18) that showed previously infected patients have detectable SARS-CoV-2 antibodies (low to moderate certainty evidence) and a decreased risk for symptomatic reinfection (high certainty evidence), the SMCP noted several gaps in the evidence:

  • Findings from these studies were unable to determine whether antibodies are primarily associated with natural immunity.
  • None of the studies assessed the association between detectable antibodies and the degree of natural immunity against COVID-19 reinfection. They also did not assess the risk for reinfection in patients who are immunocompromised and those with comorbid conditions
  • The studies were conducted prior to the emergence of the Delta and Omicron variants.
  • Evidence from these studies was insufficient to determine whether initial antibody concentrations and patient characteristics, such as race/ethnicity, modify the risk for reinfection
  • There was insufficient evidence to determine the duration of protection against COVID-19 reinfection beyond 10 months of the initial onset of infection, and variations in protection by type of SARS-CoV-2 variant were not reported.
  • Results from 3 studies suggested that previous infection with the SARS-CoV-2 Alpha variant may not confer protection against COVID-19 reinfection (insufficient evidence).

Clinical Considerations

  • The SMCP highlighted the following in regard to their updated practice points:
  • Although these practice points assessed antibody-mediated natural immune responses, neither cell-mediated immunity nor artificial immunity conferred by COVID-19 vaccination were addressed.
  • Owing to uncertainty in regard to the duration of protection conferred via natural immunity, the SMCP noted that clinicians should continue to recommend COVID-19 vaccines in clinical practice, as vaccination confers the most optimal protection against both COVID-19 infection and reinfection.

Final Remarks

Despite continued interest in natural immunity against COVID-19 infection among the scientific community, the SMPC noted that they are “retiring the ACP living, rapid practice points… from living status given the widespread availability and use of effective vaccines against SARS-CoV-2 infection in the United States.”


Qaseem A, Yost J, Etxeandia-ikobaltzeta I, et al. What is the antibody response and role in conferring natural immunity after SARS-CoV-2 infection? Rapid, living practice points from the American College of Physicians (version 2). Ann Intern Med. Published online January 25, 2022. doi:10.7326/M21-3272