Does a humoral correlate of protection exist for SARS-CoV-2? A systematic review
Bibliographic record
Abstract
Abstract Background A correlate of protection (CoP) is an immunological marker associated with protection against infection. A CoP can be used to determine whether an individual is protected from infection, evaluate candidate vaccines, guide vaccination dosing intervals and policy, and understand population-level immunity against a pathogen. Despite an urgent need, a CoP for SARS-CoV-2 is currently undefined, leaving an evidence gap for informing public health policy and adapting it appropriately as new variants of concern emerge. The objective of this study was to systematically review and assess the evidence for a humoral SARS-CoV-2 CoP. Methods and Findings We searched OVID MEDLINE, EMBASE, Global Health, Biosis Previews and Scopus from inception to January 4, 2022 and pre-prints (using NIH iSearch COVID-19 portfolio) from inception to December 31, 2021, for studies describing SARS-CoV-2 re-infection or breakthrough infection with associated antibody measures. Two reviewers independently extracted study data and performed quality assessment. Twenty-five studies were included in our systematic review. Several studies reported re-infection or breakthrough cases that occurred in the presence of robust antibody levels. Studies that compared aggregate antibody concentrations from individuals who experienced re-infection or breakthrough compared to those who remained protected did not always find differences that were statistically significant. However, several studies found an inverse relationship between antibody levels and infection incidence, risk, or viral load, and a correlation between antibody levels and vaccine efficacy (VE). Estimates of the contribution of antibody levels to VE varied from 48.5% to 94.2%, suggesting that both humoral immunity and other immune components contribute to protection. Only two studies estimated a quantitative CoP. For Ancestral SARS-CoV-2, these included 154 (95% confidence interval (CI) 42, 559) anti-S binding antibody units/mL (BAU/mL), and 28.6% (95% CI 19.2, 29.2%) of the mean convalescent antibody level following infection. One study reported a CoP for the Alpha (B.1.1.7) variant of concern of 171 (95% CI 57, 519) BAU/mL. As of our search date, no studies reported an Omicron-specific CoP. Conclusions The reviewed literature was limited by a wide variation in assay methodology and antibody targets. Few studies reported SARS-CoV-2 lineage. The studies included in our review suggest that if it exists, a SARS-CoV-2 CoP is likely relative, where higher antibody levels decrease the risk of infection, but do not eliminate it completely. More work is urgently needed in this area to establish a SARS-CoV-2 CoP and guide policy as the pandemic continues.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.063 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.011 | 0.009 |
| Bibliometrics | 0.013 | 0.012 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.004 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".