Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study

Regev‐Yochay, Gili; Lustig, Yaniv; Joseph, Gili; Gilboa, Mayan; Barda, Noam; Gens, Ilana; Indenbaum, Victoria; Halpern, Osnat; Katz-Likvornik, Shiri; Levin, Tal; Kanaaneh, Yara; Asraf, Keren; Amit, Sharon; Rubin, Carmit; Ziv, Arnona; Koren, Ravit; Mandelboim, Michal; Tokayer, Noam H; Meltzer, Lilac; Doolman, Ram; Mendelson, Ella; Alroy‐Preis, Sharon; Kreiss, Yitshak

doi:10.1016/s2666-5247(23)00012-5

Cited by 46 publications

(37 citation statements)

References 33 publications

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“…Based on crude antibody levels, a multivariable analysis, and Poisson regression model, we found a dose-dependent association of antibody levels with protection from infection and substantial symptomatic disease. Reduced odds of PCR-confirmed infection (symptomatic or asymptomatic) were observed, albeit only at high IgG (>2000 BAU) and neutralizing antibody (>1024 BAU) titers, which is approximately 4 times higher than those needed to protect against the Delta variant . These results may explain the increase in vaccine effectiveness (VE) seen after a fourth vaccine dose and the decrease in VE as time passes from this dose .…”

Section: Discussionsupporting

confidence: 65%

“…Reduced odds of PCR-confirmed infection (symptomatic or asymptomatic) were observed, albeit only at high IgG (>2000 BAU) and neutralizing antibody (>1024 BAU) titers, which is approximately 4 times higher than those needed to protect against the Delta variant. 17 These results may explain the increase in vaccine effectiveness (VE) seen after a fourth vaccine dose 6,18 and the decrease in VE as time passes from this dose. 5 Based on our results and previous literature, 5,6,17,18 we hypothesize that the fourth vaccine dose generates a rapid increase in antibody titers that may provide some initial protection, but protection gradually wanes as antibody levels decline.…”

Section: Discussionmentioning

confidence: 99%

“…17 These results may explain the increase in vaccine effectiveness (VE) seen after a fourth vaccine dose 6,18 and the decrease in VE as time passes from this dose. 5 Based on our results and previous literature, 5,6,17,18 we hypothesize that the fourth vaccine dose generates a rapid increase in antibody titers that may provide some initial protection, but protection gradually wanes as antibody levels decline. However, the introduction of bivalent vaccines targeted against both ancestral and Omicron SARS-CoV-2 could alter this decay in VE via an enhanced humoral response and increased protection against novel Omicron-related lineages, as was shown for both BA.1 and BA.5 bivalent mRNA vaccines.…”

Section: Discussionmentioning

confidence: 99%

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Factors Associated With Protection From SARS-CoV-2 Omicron Variant Infection and Disease Among Vaccinated Health Care Workers in Israel

Gilboa,

Gonen,

Barda

et al. 2023

JAMA Netw Open

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ImportanceA correlation between antibody levels and risk of infection has been demonstrated for the wild-type, Alpha, and Delta SARS-COV-2 variants. High rates of breakthrough infections by the Omicron variant emphasized the need to investigate whether the humoral response elicited by mRNA vaccines is also associated with reduced risk of Omicron infection and disease.ObjectiveTo investigate whether the high antibody levels in individuals who have received at least 3 doses of an mRNA vaccine are associated with reduced risk of Omicron infection and disease.Design, Setting, and ParticipantsThis prospective cohort study used serial real time–polymerase chain reaction (RT-PCR) and serological test data from January and May 2022 to assess the association of preinfection immunoglobin G (IgG) and neutralizing antibody titers with incidence of Omicron variant infection, incidence of symptomatic disease, and infectivity. Participants included health care workers who had received 3 or 4 doses of an mRNA COVID-19 vaccine. Data were analyzed from May to August 2022.ExposuresLevels of SARS-CoV-2 anti–receptor binding domain IgG and neutralizing antibodies.Main Outcomes and MeasuresThe main outcomes were incidence of Omicron infection, incidence of symptomatic disease, and infectivity. Outcomes were measured using SARS-COV-2 PCR and antigen testing and daily online surveys regarding symptomatic disease.ResultsThis study included 3 cohorts for 3 different analyses: 2310 participants were included in the protection from infection analysis (4689 exposure events; median [IQR] age, 50 [40-60] years; 3590 [76.6%] among female health care workers), 667 participants (median [IQR] age, 46.28 (37.44,54.8); 516 [77.4%] female) in the symptomatic disease analysis, and 532 participants (median [IQR] age, 48 [39-56] years; 403 [75.8%] female) in the infectivity analysis. Lower odds of infection were observed for each 10-fold increase in preinfection IgG (odds ratio [OR], 0.71; 95% CI, 0.56-0.90) and for each 2-fold increase in neutralizing antibody titers (OR, 0.89; 95% CI, 0.83-0.95). The odds of substantial symptomatic disease were reduced for each 10-fold increase in IgG levels (OR, 0.48; 95% CI, 0.29-0.78) and for each 2-fold increase in neutralizing antibodies levels (OR, 0.86; 95% CI, 0.76-0.96). Infectivity, assessed by mean cycle threshold value, was not significantly decreased with increasing IgG or neutralizing antibodies titers.Conclusions and RelevanceIn this cohort study of vaccinated health care workers, IgG and neutralizing antibody titer levels were associated with protection against infection with the Omicron variant and against symptomatic disease.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Factors Associated With Protection From SARS-CoV-2 Omicron Variant Infection and Disease Among Vaccinated Health Care Workers in Israel

Gilboa,

Gonen,

Barda

et al. 2023

JAMA Netw Open

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“…5,6,21 In the present study, we observed a decrease in the risk probability of Delta infection of 11% when IgG concentrations were higher than 500 BAU/mL. 22 We estimated a similar level of protection during the Delta period for the homologous (80%; two mRNA doses) and heterologous (89%; one dose of a viral vector vaccine and one dose of an mRNA vaccine) vaccination regimens when we applied the same threshold, or even about three-times higher for the hybrid immunity group (97%). Conflicting results have been reported in the case of Omicron variant regarding the value of anti-RBD IgG as a CoP.…”

Section: Discussionsupporting

confidence: 54%

Determinants of protection against SARS‐CoV‐2 Omicron BA.1 and Delta infections in fully vaccinated outpatients

Roy

Saade

Josset

et al. 2023

Journal of Medical Virology

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We aimed to evaluate the association between the humoral and cellular immune responses and symptomatic SARS‐CoV‐2 infection with Delta or Omicron BA.1 variants in fully vaccinated outpatients. Anti‐receptor binding domain (RBD) IgG levels and interferon‐gamma (IFN‐γ) release were evaluated at PCR‐diagnosis of SARS‐CoV‐2 in 636 samples from negative and positive patients during Delta and Omicron BA.1 periods. Median levels of anti‐RBD IgG in positive patients were significantly lower than in negative patients for both variants (p < 0.05). The frequency of Omicron BA.1 infection in patients with anti‐RBD IgG concentrations ≥1000 binding antibody units (BAU)/mL was 51.0% and decreased to 34.4% in patients with concentrations ≥3000 BAU/mL. For Delta infection, the frequency of infection was significantly lower when applying the same anti‐RBD IgG thresholds (13.3% and 5.3% respectively, p < 0.05). In addition, individuals in the hybrid immunity group had a 4.5 times lower risk of Delta infection compared to the homologous vaccination group (aOR = 0.22, 95% CI: [0.05−0.64]. No significant decrease in the risk of Omicron BA.1 infection was observed in the hybrid group compared to the homologous group, but the risk decreased within the hybrid group as anti‐RBD IgG titers increased (aOR = 0.08, 95% CI: [0.01−0.41], p = 0.008). IFN‐γ release post‐SARS‐CoV‐2 peptide stimulation was not different between samples from patients infected (either with Delta or Omicron BA.1 variant) or not (p > 0.05). Our results show that high circulating levels of anti‐RBD IgG and hybrid immunity were independently associated with a lower risk of symptomatic SARS‐CoV‐2 infection in outpatients with differences according to the infecting variant (www.clinicaltrials.gov; ID NCT05060939).

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“…On the other hand, this study included 100 HIV-positive subjects, all vaccinated with the same mRNA vaccine and regularly followed, who are an ideal cohort for prolonged monitoring of humoral responses and for assessing an overtime titer threshold for immunological protection from BA.5 infection [43]. Of note, in our study, the interval between booster vaccine dose and neutralizing activity testing is six months, so that giving updated information on the humoral response to the wild-type virus and to BA.5 is at a time corresponding to the administration of the fourth vaccine dose [44].…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy

et al. 2023

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Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with HIV infection on successful antiretroviral treatment and no previous SARS-CoV-2 infection. A total of 100 subjects (M/F 83/17, median age 54 years) were included in the analysis: 95 had plasma HIV RNA <40 copies/mL, the median CD4+ T cell count at the administration of the third dose was 580 cells/mm3, and the median nadir CD4+ T cell count was 258 cells/mm3. Neutralizing antibodies (NtAb) against B.1 were detectable in all the subjects, but those to BA.5 were only detected in 88 (p < 0.001). The median NtAb titer to B.1 was significantly higher than that to BA.5 (393 vs. 60, p < 0.0001), and there was a strong positive correlation between the paired measurements (p < 0.0001). Linear regression on a subset of 87 patients excluding outlier NtAb titers showed that 48% of the changes in NtAb titers to BA.5 are related to the changes in value titers to B.1. SARS-CoV-2 variants evolve rapidly, challenging the efficacy of vaccines, and data on comparative NtAb responses may help in tailoring intervals between vaccine doses and in predicting vaccine efficacy.

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Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study

Cited by 46 publications

References 33 publications

Factors Associated With Protection From SARS-CoV-2 Omicron Variant Infection and Disease Among Vaccinated Health Care Workers in Israel

Factors Associated With Protection From SARS-CoV-2 Omicron Variant Infection and Disease Among Vaccinated Health Care Workers in Israel

Determinants of protection against SARS‐CoV‐2 Omicron BA.1 and Delta infections in fully vaccinated outpatients

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy

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