Does a humoral correlate of protection exist for SARS-CoV-2? A systematic review

Background A correlate of protection (CoP) is an immunological marker associated with protection against infection. Despite an urgent need, a CoP for SARS-CoV-2 is currently undefined. Objectives Our objective was to review the evidence for a humoral correlate of protection for SARS-CoV-2, including variants of concern. Methods We searched OVID MEDLINE, EMBASE, Global Health, Biosis Previews and Scopus to January 4, 2022 and pre-prints (using NIH iSearch COVID-19 portfolio) 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. Results Twenty-five studies were included in our systematic review. Two studies examined the correlation of antibody levels to VE, and reported values from 48.5% to 94.2%. Similarly, several studies found an inverse relationship between antibody levels and infection incidence, risk, or viral load, suggesting that both humoral immunity and other immune components contribute to protection. However, individual level data suggest infection can still occur in the presence of high levels of antibodies. 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. No studies have yet reported an Omicron-specific CoP. Conclusions Our review suggests that 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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19047 20 ((vaccinated or immunized or immunised) adj5 (infected or infection* or contracted or acquired or acquisition or caught or got* or transmi* or spread* or outbreak* or cluster* or communicab* or contagious* or epidemic* or occurrence or case or cases)).ab,kf,kw,ti. 8545 21 ((vaccinated or immunized or immunised) adj10 (person or persons or people or man or men or woman or women or adult or adults or patient or patients or individual or individuals or responder or responders or practitioner* or staff or personnel or worker* or employee* or provider* or technician* or clinician* or doctor* or nurse or nurses or paramedic* or physician* or hospitalist* or pharmacist*) adj10 (infected or infection* or contracted or acquired or acquisition or caught or got* or transmi* or spread* or outbreak* or cluster* or communicab* or contagious* or epidemic* or occurrence or case or cases)).ab,kf,kw,ti.
2764 22 ((escape or escapes or escaped or escaping or evade or evades or evaded or evading or evasion) adj5 ("Ad26.COV2.S" or AZD1222 or BNT162* or ChAdOx1* or Comirnaty or immunis* or immuniz* or "JNJ-78436735" or "mrna-1273*" or Novavax or NVX-CoV2373 or PittCoVacc* or postvaccin* or postimmunis* or postimmuniz* or reimmunis* or reimmuniz* or revacciat* or tozinameran or vaccin*)).ab,kf,kw,ti. 25 ((decay* or declin* or decreas* or impair* or duration or fail* or fall* or "go* down" or lack or lacks or lacked or lacking or lose or loses or losing or loss or lost or low or lower* or lesser* or poor or poorer* or "adversely affect*" or reduc*) adj5 (protect* or effectiv* or immunity or "immune respon*" or antibod* or sero*)).kf,kw,ti. and (infected or infection* or contracted or acquired or acquisition or caught or got* or transmi* or spread* or outbreak* or cluster* or communicab* or contagious* or epidemic* or occurrence or case or cases).ab,kf,kw,ti. 26 ((decay* or declin* or decreas* or impair* or duration or fail* or fall* or "go* down" or lack or lacks or lacked or lacking or lose or loses or losing or loss or lost or low or lower* or lesser* or poor or poorer* or "adversely affect*" or reduc*) adj5 (protect* or effectiv* or immunity or "immune respon*" or antibod* or sero*)).ab,kf,kw,ti. and (infected or infection* or contracted or acquired or acquisition or caught or got* or transmi* or spread* or outbreak* or cluster* or communicab* or contagious* or epidemic* or occurrence or case or cases).kf,kw,ti.

Records source Records
Records identified through database searching 5047 Duplicates removed by database 0 Duplicates removed by bibliographic management software 4,159
27 ((decay* or declin* or decreas* or impair* or duration or fail* or fall* or "go* down" or lack or lacks or lacked or lacking or lose or loses or losing or loss or lost or low or lower* or lesser* or poor or poorer* or "adversely affect*" or reduc*) adj5 (protect* or effectiv* or immunity or "immune respon*" or antibod* or sero*)).ab,ti,hw. and (infected or infection* or contracted or acquired or acquisition or caught or got* or transmi* or spread* or outbreak* or cluster* or communicab* or contagious* or epidemic* or occurrence or case or cases).hw,ti.

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Literature Search: COVID-19 antibody correlates of protection -supplementary databases

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Search results Results attached as a CSV Excel file

Records source Records
Records identified through database searching 1398 Duplicates removed by database 0 Duplicates removed by bibliographic management software 409 Total records after duplicates removed 989

Records source Records
Records identified through database searching 655 Duplicates removed by database 0 Duplicates removed by bibliographic management software 521 Total records after duplicates removed 134 Search strategies EMBASE Embase <1974 to 2021 Week 52>