CoChat
Sign Up
Cited by 69SARS-CoV-2 and COVID-19 ResearchImmune responses and vaccinationsCOVID-19 Clinical Research Studies

COVID 19 Vaccines: Should we fear ADE?

Open access
Halstead, Scott B, Katzelnick, Leah·2020·The Journal of Infectious Diseases
DOI 10.1093/infdis/jiaa518PMC PMC7454712
Open this paper in CoChat — free accountOpen PDF

Abstract

Might COVID-19 vaccines sensitize humans to antibody-dependent enhanced (ADE) breakthrough infections? This is unlikely because coronavirus diseases in humans lack the clinical, epidemiological, biological, or pathological attributes of ADE disease exemplified by dengue viruses (DENV). In contrast to DENV, SARS and MERS CoVs predominantly infect respiratory epithelium, not macrophages. Severe disease centers on older persons with preexisting conditions and not infants or individuals with previous coronavirus infections. Live virus challenge of animals given SARS or MERS vaccines resulted in vaccine hypersensitivity reactions (VAH), similar to those in humans given inactivated measles or respiratory syncytial virus vaccines. Safe and effective COVID-19 vaccines must avoid VAH.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/infdis/jiaa518

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Current evidence suggests SARS-CoV-2 does not productively infect macrophages, making infection enhancement unlikely.

    “Current evidence indicates that SARS-CoV-2 does not productively infect macrophages, making enhancement of infection unlikely, and ADE and VAERD have so far not been demonstrated for SARS-CoV-2 (refs175,176).”

    From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [175]

  • ADE and VAERD have not yet been demonstrated for SARS-CoV-2.

    “Current evidence indicates that SARS-CoV-2 does not productively infect macrophages, making enhancement of infection unlikely, and ADE and VAERD have so far not been demonstrated for SARS-CoV-2 (refs175,176).”

    From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [175]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 48

  1. Saif LJ. Animal coronavirus vaccines: lessons for SARS. Dev Biol 2004; 119:129-40.
  2. Pedersen NC. An update on feline infectious peritonitis: vi- rology and immunopathogenesis. Vet J 2014; 201:123-32.
  3. Arvin AM, Fink K, Schmid MA, et al. A perspective on po- tential antibody-dependent enhancement of SARS-CoV-2. Nature 2020; 584:353-63.
  4. Halstead SB, Mahalingam S, Marovich MA, Ubol S, Mosser DM. Intrinsic antibody-dependent enhance- ment of microbial infection in macrophages: disease reg- ulation by immune complexes. Lancet Infect Dis 2010; 10:712-22.
  5. Ubol S, Halstead SB. How innate immune mechanisms con- tribute to antibody-enhanced viral infections. Clin Vaccine Immunol 2010; 17:1829-35.
  6. Fulginiti VA, Eller JJ, Downie AW, Kempe CH. Altered re- activity to measles virus. Atypical measles in children pre- viously immunized with inactivated measles virus vaccines. JAMA 1967; 202:1075-80.
  7. Chin J, Magoffin RL, Shearer LA, Schieble JH, Lennette EH. Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric popu- lation. Am J Epidemiol 1969; 89:449-63.
  8. Polack FP, Auwaerter PG, Lee SH, et al. Production of atyp- ical measles in rhesus macaques: evidence for disease me- diated by immune complex formation and eosinophils in the presence of fusion-inhibiting antibody. Nat Med 1999; 5:629-34.
  9. Tseng CT, Sbrana E, Iwata-Yoshikawa N, et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One 2012; 7:e35421.
  10. Bolles M, Deming D, Long K, et al. A double-inactivated severe acute respiratory syndrome coronavirus vaccine pro- vides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge. J Virol 2011; 85:12201-15.
  11. Wang SF, Tseng SP, Yen CH, et al. Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins. Biochem Biophys Res Commun 2014; 451:208-14.
  12. Lee N, Chan PK, Ip M, et al. Anti-SARS-CoV IgG response in relation to disease severity of severe acute respiratory syndrome. J Clin Virol 2006; 35:179-84.
  13. Jaume M, Yip MS, Cheung CY, et al. Anti-severe acute res- piratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH-and cys- teine protease-independent FcγR pathway. J Virol 2011; 85:10582-97.
  14. Sridhar S, Luedtke A, Langevin E, et al. Effect of dengue serostatus on dengue vaccine safety and efficacy. N Engl J Med 2018; 379:327-40.
  15. Borges MB, Marchevsky RS, Carvalho Pereira R, et al. Detection of post-vaccination enhanced dengue virus infection in macaques: An improved model for early assessment of dengue vaccines. PLoS Pathog 2019; 15:e1007721.
  16. Vaughn DW, Green S, Kalayanarooj S, et al. Dengue viremia titer, antibody response pattern, and virus serotype corre- late with disease severity. J Infect Dis 2000; 181:2-9.
  17. Aye KS, Charngkaew K, Win N, et al. Pathologic highlights of dengue hemorrhagic fever in 13 autopsy cases from Myanmar. Hum Pathol 2014; 45:1221-33.
  18. Peiris JS, Yuen KY, Osterhaus AD, Stöhr K. The severe acute respiratory syndrome. N Engl J Med 2003; 349:2431-41.
  19. Balsitis SJ, Coloma J, Castro G, et al. Tropism of dengue virus in mice and humans defined by viral nonstructural protein 3-specific immunostaining. Am J Trop Med Hyg 2009; 80:416-24.
  20. Halstead SB. Observations related to pathogenesis of dengue hemorrhagic fever. VI. Hypotheses and discussion. Yale J Biol Med 1970; 42:350-62.
  21. Olkowski S, Forshey BM, Morrison AC, et al. Reduced risk of disease during postsecondary dengue virus infections. J Infect Dis 2013; 208:1026-33.
  22. Halstead SB, Nimmannitya S, Cohen SN. Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered. Yale J Biol Med 1970; 42:311-28.
  23. Nisalak A, Halstead SB, Singharaj P, Udomsakdi S, Nye SW, Vinijchaikul K. Observations related to pathogenesis of dengue hemorrhagic fever. III. Virologic studies of fatal dis- ease. Yale J Biol Med 1970; 42:293-310.
  24. Rodriguez-Roche R, Sanchez L, Burgher Y, et al. Virus role during intraepidemic increase in dengue disease severity. Vector Borne Zoonotic Dis 2011; 11:675-81.
  25. Liu L, Wei Q, Lin Q, et al. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI insight 2019; 4:e123158.
  26. Sangkawibha N, Rojanasuphot S, Ahandrik S, et al. Risk factors in dengue shock syndrome: a prospective epidemio- logic study in Rayong, Thailand. I. The 1980 outbreak. Am J Epidemiol 1984; 120:653-69.
  27. Simmons CP, Chau TN, Thuy TT, et al. Maternal antibody and viral factors in the pathogenesis of dengue virus in in- fants. J Infect Dis 2007; 196:416-24.
  28. Anderson KB, Gibbons RV, Cummings DA, et al. A shorter time interval between first and second dengue infections is associated with protection from clinical illness in a school- based cohort in Thailand. J Infect Dis 2014; 209:360-8.
  29. Halstead SB. Neutralization and antibody-dependent enhance- ment of dengue viruses. Adv Virus Res 2003; 60:421-67.
  30. Cohen SN, Halstead SB. Shock associated with dengue infection. I. Clinical and physiologic manifestations of dengue hemorrhagic fever in Thailand, 1964. J Pediatrics 1966; 68:448-56.
  31. Halstead SB, Chow JS, Marchette NJ. Immunological enhance- ment of dengue virus replication. Nat New Biol 1973; 243:24-6.
  32. Halstead SB. In vivo enhancement of dengue virus infec- tion in rhesus monkeys by passively transferred antibody. J Infect Dis 1979; 140:527-33.
  33. Glasner DR, Puerta-Guardo H, Beatty PR, Harris E. The good, the bad, and the shocking: the multiple roles of dengue virus nonstructural protein 1 in protection and pathogenesis. Annu Rev Virol 2018; 5:227-53.
  34. Suwarto S, Sasmono RT, Sinto R, Ibrahim E, Suryamin M. Association of endothelial glycocalyx and tight and adherens junctions with severity of plasma leakage in dengue infec- tion. J Infect Dis 2017; 215:992-9.
  35. Glasner DR, Ratnasiri K, Puerta-Guardo H, Espinosa DA, Beatty PR, Harris E. Dengue virus NS1 cytokine- independent vascular leak is dependent on endothelial glycocalyx components. PLoS Pathog 2017; 13:e1006673.
  36. Chau TN, Quyen NT, Thuy TT, et al. Dengue in Vietnamese in- fants-results of infection-enhancement assays correlate with age- related disease epidemiology, and cellular immune responses correlate with disease severity. J Infect Dis 2008; 198:516-24.
  37. Weiss RC, Scott FW. Pathogenesis of feline infectious per- itonitis: nature and development of viremia. Am J Vet Res 1981; 42:382-90.
  38. Nicholls JM, Butany J, Poon LL, et al. Time course and cel- lular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS. PLoS Med 2006; 3:e27.
  39. Lau YL, Peiris JS. Pathogenesis of severe acute respiratory syndrome. Curr Opin Immunol 2005; 17:404-10.
  40. Liu WJ, Zhao M, Liu K, et al. T-cell immunity of SARS- CoV: implications for vaccine development against MERS- CoV. Antiviral Res 2017; 137:82-92.
  41. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med 2020; 383:120-8.
  42. Bikdeli B, Madhavan MV, Jimenez D, et al; Global COVID- 19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and thrombotic or thromboem- bolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75:2950-73.
  43. Channappanavar R, Perlman S. Pathogenic human coro- navirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017; 39:529-39.
  44. Hubert B, Halstead SB. Dengue 1 virus and dengue hem- orrhagic fever, French Polynesia, 2001. Emerg Infect Dis 2009; 15:1265-70.
  45. Clay C, Donart N, Fomukong N, et al. Primary severe acute respiratory syndrome coronavirus infection limits replication but not lung inflammation upon homologous rechallenge. J Virol 2012; 86:4234-44.
  46. Horstmann DM, Liebhaber H, Le Bouvier GL, Rosenberg DA, Halstead SB. Rubella: reinfection of vac- cinated and naturally immune persons exposed in an epi- demic. N Engl J Med 1970; 283:771-8.
  47. Eyal N, Lipsitch M, Smith PG. Human challenge studies to accelerate coronavirus vaccine licensure. J Infect Dis 2020; 221:1752-6.
  48. Halstead SB. An urgent need for "common cold units" to study novel coronavirus disease (COVID-19). Am J Trop Med Hyg 2020; 102:1152-3.

Cited by

Sorted by citations

Authors
Halstead, S. B., & Katzelnick, L.
Affiliations
  • University of California, Berkeley (US)
  • University of Florida (US)
Corresponding author
Halstead, Scott B
ORCID
Venue
The Journal of Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2020-08-12
Volume
222
Issue
12
Pages
1946-1950
ISSN
  • 0022-1899 (ISSN-L)
  • 1537-6613
DOI
10.1093/infdis/jiaa518
PMC
PMC7454712
OpenAlex
W3048746618
Cited by
69
References
0
Citations by year
2026: 1 · 2025: 4 · 2024: 3 · 2023: 10 · 2022: 19 · 2021: 28 · 2020: 4
FWCI
0.72
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • The Journal of Infectious Diseases (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
COVID-19 vaccines, antibody-dependent enhancement, vaccine adverse events, SARS-CoV-2, dengue virus, breakthrough infection, SARS-CoV, MERS-CoV, vaccine safety, RSV vaccine, measles vaccine
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, Animals, Humans, Hypersensitivity, Antibody-Dependent Enhancement, Severe acute respiratory syndrome-related coronavirus, Dengue Vaccines

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review