Risk of Reinfection From SARS-CoV-2 – An Update of an Antibody Response Following SARS-CoV-2 Infection and Implications for Immunity: A Living Rapid Review

Abstract

Key Questions1. What is the prevalence, level, and durability of detectable anti-SARS-CoV-2 antibodies among adults infected with or recovered from reverse transcription polymerase chain reaction (RT-PCR) -diagnosed SARS-CoV-2 infection? a. Do the levels and durability of detectable antibodies vary by patient characteristics (e.g., age, sex, race/ethnicity, and comorbidities), COVID-19 severity, presence of symptoms, time from symptom onset, or as measured by different types of immunoassays (e.g., immunoassay sensitivity/specificity)? 2. Do anti-SARS-CoV-2 antibodies confer natural immunity against reinfection? a. Does conferred immunity vary by factors such as initial antibody levels, patient characteristics, presence of symptoms, or severity of disease? b. Is there a threshold level of detectable anti-SARS-CoV-2 antibodies necessary to confer natural immunity, and if so, does this threshold vary by patient characteristics (e.g., age, sex, race/ethnicity, and comorbidities)? 3. If anti-SARS-CoV-2 antibodies confer natural immunity against reinfection, how long does this immunity last? a. Does immunity vary by factors such as initial antibody levels, patient characteristics, presence of symptoms, or severity of disease? 4. What are the unintended consequences of antibody testing after SARS-CoV-2 infection? Key Question 1: Prevalence, Levels, and Duration of Detectable Antibodies in SARS-CoV-2 Infection Summary prevalence estimates are presented in Table 1, and an overview of how antibody levels trend over time is presented in Table 2. Detailed prevalence results from seroprevalence, cross-sectional, and cohort studies are presented in Appendix Table C-3 and prevalence results from immunoassay validation studies are presented in Appendix Table C-4. Strength of evidence assessments are summarized in Appendix E. Table 1. IgM, IgG, IgA and neutralizing antibody prevalence Antibody Subtype Peak Prevalence Estimate (%) Number of Studies; Total Number (N) of RT-PCR+ Participants IgM Median 80* (Range: 9-98) when measured approximately 20 days post-symptom onset or RT-PCR diagnosis

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)

“…The evidence update ( 5 , 6 ) identified 18 new studies ( 8–25 ) informing key questions 2, 2a, and 3, for which there were previously no studies that met the inclusion criteria in version 1 ( 3 ). These studies were initiated before the emergence of the Delta and Omicron variants and before the U.S. Food and Drug Administration's emergency use authorization of vaccines late in 2020 ( 5 , 6 ).…”

“…The evidence update ( 5 , 6 ) identified 18 new studies ( 8–25 ) informing key questions 2, 2a, and 3, for which there were previously no studies that met the inclusion criteria in version 1 ( 3 ). These studies were initiated before the emergence of the Delta and Omicron variants and before the U.S. Food and Drug Administration's emergency use authorization of vaccines late in 2020 ( 5 , 6 ). The new studies compared the risk for symptomatic reinfection (as a primary outcome) among adults with a recent SARS-CoV-2 infection with the risk for infection among adults without a recent infection, with “recent” defined as within 7 months of initial SARS-CoV-2 infection.…”

“…The following practice points are based on the current best available evidence. The Figure , Table 2 , and the accompanying systematic review ( 5 , 6 ) summarize changes in the findings. Table 3 presents clinical considerations, and Table 4 identifies evidence gaps.…”

“… * Observational studies include studies estimating seroprevalence among a given population that includes a small subpopulation known to have SARS-CoV-2 infection; cross-sectional or cohort studies characterizing the antibody response among adults with SARS-CoV-2 infection; and large, population-based observational (cohort, case–control) studies comparing risk for reinfection in adults with and without recent SARS-CoV-2 infection ( 3 , 5 , 6 ). Immunoassay validation studies include those validating the diagnostic performance of 1 or more immunoassays ( 3 ).…”

“…This is version 2 of the ACP practice points, which serves to update version 1, published on 16 March 2021 ( 3 , 4 ). It is based on a focused update of a living, rapid, systematic review conducted by the Portland VA Research Foundation and funded by the Agency for Healthcare Research and Quality ( 5 , 6 ). The SMPC developed these practice points according to ACP's practice points development process, details of which can be found in ACP's methods paper ( 7 ).…”