A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity

  1. Angkana T. Huang
  2. Bernardo Garcia-Carreras
  3. Matt D. T. Hitchings
  4. Bingyi Yang
  5. Leah C. Katzelnick
  6. Susan M. Rattigan
  7. Brooke A. Borgert
  8. Carlos A. Moreno
  9. Benjamin D. Solomon
  10. Luke Trimmer-Smith
  11. Veronique Etienne
  12. Isabel Rodriguez-Barraquer
  13. Justin Lessler
  14. Henrik Salje
  15. Donald S. Burke
  16. Amy Wesolowski
  17. Derek A. T. Cummings

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV, MERS-CoV and endemic human coronaviruses (HCoVs). We reviewed 2,452 abstracts and identified 491 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.

Article activity feed

  1. Version published to 10.1038/s41467-020-18450-4
  2. ScreenIT

    SciScore for 10.1101/2020.04.14.20065771: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    Researchers have used assays of both types to characterize antibody activity by antibody class ( i.e. IgG , IgM , IgA) .
    IgM , IgA
    suggested: None
    Many studies reported an immune response , characterized by a robust increment of antibody titers for HCoV-229E , MERS-CoV , SARS-CoV1 , and SARS-CoV-2 after the second or third weeks following the onset of illness8,23–30 .
    SARS-CoV1
    suggested: None
    Callow et al.8 found among experimental infections with HCoV-229E that after peaks in IgG and IgA , antibody levels waned and between 11 weeks and 1 year post inoculation were at similar levels to those found in inoculated but uninfected patients .
    IgA
    suggested: None
    Several studies found that cases of varying severity ( e.g. , asymptomatic , mild , and severe ) developed detectable antibodies against HCoV-229E , SARS-CoV-1 , SARS-CoV-2 , and MERSCoV33,41–44 .
    SARS-CoV-2
    suggested: (Sino Biological Cat# 40143-R019, AB_2827973)
    Figure 4 provides a broad sense for trajectories of antibodies ( also see Figures S2 and S3) .
    S3
    suggested: None
    Healthy individuals with antibodies to HCoV-229E , HCoV-OC43 , and other endemic HCoVs rarely had detectable antibodies that bound SARS-CoV-1 infected cells or SARS-CoV-1 N protein68,73,74 .
    HCoV-OC43
    suggested: None
    Blood donors in Southern China ( n=152 ) and Saudi Arabia ( n=130 ) did not have detectable binding ( IFA ) or neutralizing antibodies to either MERS-CoV or SARS-CoV-176,77 .
    SARS-CoV-176,77
    suggested: None
    Some SARS patients also showed a rise in antibodies to HCoV-229E and HCoV-OC43 N protein73 and HCoV-NL6379 .
    HCoV-OC43 N protein73
    suggested: None
    Among SARS-CoV-1 patients ( n=28) , 60 % had detectable IFA titers to MERS-CoV and 25 % had anti-MERS-CoV neutralizing antibodies .
    anti-MERS-CoV neutralizing antibodies .
    suggested: None
    A subset of slaughterhouse workers in Saudi Arabia had antibodies to MERS-CoV by IFA as well as to pandemic HCoVs , but none had reactivity to SARS-CoV-1 spike protein .
    SARS-CoV-1 spike protein .
    suggested: None
    Regarding regions of the spike protein that may induce antibodies with enhancement effects , both anti-S1a and anti-S1b mAbs showed mild to moderate effects103 .
    anti-S1b
    suggested: None
    Anti-S2 IgG antibodies targeting uninfected lung epithelial cells ( A549 ) were detected in SARS-CoV-1 patients after twenty days post-symptom onset106 , a reactivity not seen in serum from healthy individuals and non-SARS-CoV-1 pneumonia patients
    A549
    suggested: None
    In mice108 and humans109 , there is evidence of anti-N antibodies that cross react with IL-11 , an anti-inflammatory cytokine expressed in many tissues , including lung and bone marrow .
    anti-N
    suggested: None
    Preliminary studies on SARS-CoV-2 point to a possibly contrasting pattern to MERS-CoV: while IgM antibodies appear at the same time in severe and non-severe cases, IgG appears sooner in severe cases33.
    MERS-CoV: while IgM
    suggested: None
    Not all of these studies reported a cutoff for the assay used; in those that did, two thirds of patients with mild symptoms had detectable or positive IgG antibodies at six months and one year, while all patients with severe symptoms had detectable IgG antibodies at the same points in time (Table 1).
    positive IgG
    suggested: None
    Another prospective study51 reported detection of pre-existing neutralizing antibodies among medical students who had virus isolation (67%, n=8/12) or seroconversion to HCoV-229E (25%, n=3/12).
    HCoV-229E
    suggested: None
    Individuals experiencing natural infections with HCoV-OC43 or HCoV-229E did not have detectable antibodies in acute or convalescent samples against SARS-CoV-1 (to N protein72; by IFA or neutralization39).
    SARS-CoV-1
    suggested: None
    A series of studies by Yip et al. demonstrated that opsonization of anti-spike antibodies allowed SARS-CoV-1 to enter non-ACE2 expressing immune cells that bear Fc--RII (CD32)99,100.
    anti-spike
    suggested: None
    Regarding regions of the spike protein that may induce antibodies with enhancement effects, both anti-S1a and anti-S1b mAbs showed mild to moderate effects103.
    anti-S1a
    suggested: None
    Anti-S2 IgG antibodies targeting uninfected lung epithelial cells (A549) were detected in SARS-CoV-1 patients after twenty days post-symptom onset106, a reactivity not seen in serum from healthy individuals and non-SARS-CoV-1 pneumonia patients.
    Anti-S2 IgG
    suggested: None
    Presence of anti-S2 antibodies also increased the binding of immune cells (PBMCs) to A549 cells treated with IFN-, replicating the conditions under which a cytokine storm would be observed.
    anti-S2
    suggested: None
    In mice108 and humans109, there is evidence of anti-N antibodies that cross react with IL-11, an anti-inflammatory cytokine expressed in many tissues, including lung and bone marrow.
    IL-11
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    A separate study demonstrated colocalization of anti-S2 Abs collected from serum of SARS patients ≥50 days post-fever onset with annexin A2 and immunoprecipitated annexin A2 on A549 cell surfaces .
    A549
    suggested: NCI-DTP Cat# A549, CVCL_0023
    The Alphacoronaviruses include two major human coronaviruses, HCoV-229E and HCoV-NL63.
    HCoV-229E
    suggested: None
    Some SARS patients also showed a rise in antibodies to HCoV-229E and HCoV-OC43 N protein73 and HCoV-NL6379.
    HCoV-OC43 N protein73
    suggested: None
    Software and Algorithms
    SentencesResources
    Additionally , we identified articles that may be relevant from the reference list of other articles identified by our PubMed searches .
    PubMed
    suggested: (PubMed, SCR_004846)
    Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs).
    SARS-CoV-2
    suggested: (Sino Biological Cat# 40143-R019, AB_2827973)

    Results from OddPub: Thank you for sharing your data.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.04.14.20065771v1 on medRxiv