IgG targeting distinct seasonal coronavirus- conserved SARS-CoV-2 spike subdomains correlates with differential COVID-19 disease outcomes

Garrido, José; Medina, Matías A.; Bravo, Felipe; McGee, Sasha; Fuentes-Villalobos, Francisco; Calvo, Mario; Pinos, Yazmín; Bowman, James W.; Bahl, Christopher D.; Barría, María Inés; Brachman, Rebecca A.; Alvarez, Raymond

doi:10.1016/j.celrep.2022.110904

Cited by 13 publications

(15 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recently, pre-existing IgG targeting several seasonal coronavirus-conserved SARS-CoV-2 spike subdomains have been correlated with differential COVID-19 disease outcomes and authors suggested that the severity of disease depend on epitope targeting by humoral recall response. Pre-existing IgG targeting the S2’FP region of SARS-CoV-2 are predictors of more severe COVID-19 than IgG targeting HR2, 5’fHR” or RDB region [49] . More studies are necessary to understand if ADE is involved in these effects.…”

Section: Sars-cov-2 and Ade: Mechanisms And Evidencementioning

confidence: 92%

Non-neutralizing antibodies: Deleterious or propitious during SARS-CoV-2 infection?

Zanella

Antoni

Marchese

et al. 2022

International Immunopharmacology

View full text Add to dashboard Cite

Section: Sars-cov-2 and Ade: Mechanisms And Evidencementioning

confidence: 92%

Non-neutralizing antibodies: Deleterious or propitious during SARS-CoV-2 infection?

Zanella

Antoni

Marchese

et al. 2022

International Immunopharmacology

View full text Add to dashboard Cite

“…Indeed, Sagar et al showed that less-severe COVID-19 is associated with recent endemic coronavirus infections likely because of pre-existing and still active immune responses [33]. Garrido et al, by characterising anti-spike IgG responses in 28 non-hospitalised convalescent individuals across a spectrum of COVID-19 severity (13 with mild and 15 with severe disease) and 20 COVID-19 negative donors, demonstrated that humoral memory responses against seasonal coronaviruses contribute to COVID-19 disease severity, conferring either protection or risk, depending on epitope targeting [34].…”

Section: Discussionmentioning

confidence: 99%

Effects of Antibody Responses to Pre-Existing Coronaviruses on Disease Severity and Complement Activation in COVID-19 Patients

et al. 2022

View full text Add to dashboard Cite

The severity of coronavirus disease 2019 (COVID-19) may be influenced by pre-existing immune responses against endemic coronaviruses, but conflicting data have been reported. We studied 148 patients who were hospitalised because of a confirmed diagnosis of COVID-19, classified mild in 58, moderate in 44, and severe in 46. The controls were 27 healthy subjects. At admission, blood samples were collected for the measurement of biomarkers of disease severity and levels of the IgG against the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and pre-existing coronaviruses OC43, HKU1, NL63 and 229E. Higher levels of IgG antibodies against the RBD of pre-existing coronavirus (with the highest significance for anti-HKU1 IgG, p = 0.01) were found in patients with mild disease, compared with those with moderate or severe disease. Multivariable logistic regression confirmed the association of high levels of antibodies to pre-existing coronavirus with mild disease and showed their associations with low levels of the complement activation marker SC5b-9 (p range = 0.007–0.05). High levels of anti-NL63 antibodies were associated with low levels of the coagulation activation marker D-dimer (p = 0.04), while high levels of IgG against 229E were associated with low levels of the endothelial activation marker von Willebrand factor (p = 0.05). Anti-SARS-CoV-2-neutralising activity of plasma positively correlated with anti-SARS-CoV-2 IgG (r = 0.53, p = 0.04) and with anti-HKU1 IgG (r = 0.51, p = 0.05). In hospitalised patients with COVID-19, high levels of antibodies to pre-existing coronaviruses are associated with mild disease, suggesting that their measurement could be useful in predicting the severity of the disease.

show abstract

“…Garrido et al . demonstrated a correlation of IgG targeting different immunodominant conserved S2 regions with COVID-19 severity: Abs against heptad repeat-2 and S2’ fusion peptide correlated with milder and more severe disease, respectively (69); the functional aspects of these anti-S2 Abs are yet to be evaluated. Further studies also are warranted to focus on the activities of pre-existing and SARS-CoV-2-induced S2-specific Abs, including neutralization, Fab affinity, Fc glycosylation, and affinity for Fc receptors and complement, in patients with different disease severity and after COVID-19 vaccination.…”

Section: Discussionmentioning

confidence: 99%

“…Fc-mediated Ab functions also have been associated with COVID-19 severity. Abs-mediated FcγRIIa and FcγRIIIa activation positively correlated with symptom severity among ambulatory New York patients at 1-2 months post-disease onset (69). Additionally, IgG Fc glycome composition was shown to predict disease severity, with patients with a poor outcome having, at diagnosis, IgG deficient in galactosylation and sialylation and more bis-GlcNAc structures (13).…”

Section: Discussionmentioning

confidence: 99%

“…Neutralizing mAbs against S2 have been reported, such as 3A3 specific for a conserved epitope in the hinge region between the heptad repeat-1 helix and the central helix(67) and B1 recognizing the beta-hairpin region(68), although the prevalence of these Abs in COVID-19 patients is unknown. Garrido et al demonstrated a correlation of IgG targeting different immunodominant conserved S2 regions with COVID-19 severity: Abs against heptad repeat-2 and S2' fusion peptide correlated with milder and more severe disease, respectively(69); the functional aspects of these anti-S2Abs are yet to be evaluated. Further studies also are warranted to focus on the activities of pre-existing and SARS-CoV-2-induced S2-specific Abs, including neutralization, Fab affinity, Fc glycosylation, and affinity for Fc receptors and complement, in patients with different disease severity and after COVID-19 vaccination.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Immune Profiles to Distinguish Hospitalized Versus Ambulatory Covid-19 Cases in Older Patients

Klingler

Lambert

Bandrés

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: A fraction of COVID-19 patients develops severe disease requiring hospitalization, while the majority, including high-risk individuals, experience mild symptoms. Severe disease has been associated with higher levels of antibodies and inflammatory cytokines, but the association has often resulted from comparison of patients with diverse demographics and comorbidity status. This study examined patients with defined demographic risk factors for severe COVID-19 who developed mild vs. severe COVID-19. Methods: This study evaluated hospitalized vs. ambulatory COVID-19 patients in the James J. Peters VA Medical Center, Bronx, NY. This cohort presented demographic risk factors for severe COVID-19: median age of 63, >80% male, >85% black and/or Hispanic. Sera were collected four to 243 days after symptom onset and evaluated for binding and functional antibodies as well as 48 cytokines/chemokines. Findings: Ambulatory and hospitalized patients showed no difference in SARS-CoV-2-specific antibody levels and functions. However, a strong correlation between anti-S2 antibody levels and the other antibody parameters was observed in hospitalized but not in ambulatory cases. Cytokine/chemokine levels also revealed differences, with notably higher IL-27 levels in hospitalized patients. Hence, among the older, mostly male patients studied here, SARS-CoV-2-specific antibody levels and functions did not distinguish hospitalized and ambulatory cases but a discordance in S2-specific antibody responses was noted in ambulatory patients, and elevated levels of specific cytokines were maintained in convalescent sera of hospitalized cases. Interpretation: The data indicate that antibodies against the relatively conserved S2 spike subunit and immunoregulatory cytokines such as IL-27 are potential immune determinants of COVID-19.

show abstract

IgG targeting distinct seasonal coronavirus- conserved SARS-CoV-2 spike subdomains correlates with differential COVID-19 disease outcomes

Cited by 13 publications

References 72 publications

Non-neutralizing antibodies: Deleterious or propitious during SARS-CoV-2 infection?

Non-neutralizing antibodies: Deleterious or propitious during SARS-CoV-2 infection?

Effects of Antibody Responses to Pre-Existing Coronaviruses on Disease Severity and Complement Activation in COVID-19 Patients

Immune Profiles to Distinguish Hospitalized Versus Ambulatory Covid-19 Cases in Older Patients

Contact Info

Product

Resources

About