RESUMEN
Genetic polymorphisms have been linked to the differential waning of vaccine-induced immunity against COVID-19 following vaccination. Despite this, evidence on the mechanisms behind this waning and its implications for vaccination policy remains limited. We hypothesize that specific gene variants may modulate the development of vaccine-initiated immunity, leading to impaired immune function. This study investigates genetic determinants influencing the sustainability of immunity post-mRNA vaccination through a genome-wide association study (GWAS). Utilizing a hospital-based, test negative case-control design, we enrolled 1,119 participants from the Taiwan Precision Medicine Initiative (TPMI) cohort, all of whom completed a full mRNA COVID-19 vaccination regimen and underwent PCR testing during the Omicron outbreak. Participants were classified into breakthrough and protected groups based on PCR results. Genetic samples were analyzed using SNP arrays with rigorous quality control. Cox regression identified significant single nucleotide polymorphisms (SNPs) associated with breakthrough infections, affecting 743 genes involved in processes such as antigenic protein translation, B cell activation, and T cell function. Key genes identified include CD247, TRPV1, MYH9, CCL16, and RPTOR, which are vital for immune responses. Polygenic risk score (PRS) analysis revealed that individuals with higher PRS are at greater risk of breakthrough infections post-vaccination, demonstrating a high predictability (AUC = 0.787) in validating population. This finding confirms the significant influence of genetic variations on the durability of immune responses and vaccine effectiveness. This study highlights the importance of considering genetic polymorphisms in evaluating vaccine-induced immunity and proposes potential personalized vaccination strategies by tailoring regimens to individual genetic profiles.
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Vacunas contra la COVID-19 , COVID-19 , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Femenino , Persona de Mediana Edad , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Estudios de Casos y Controles , Adulto , Eficacia de las Vacunas , Anciano , Vacunas de ARNm , Taiwán , Vacunación , Medicina de Precisión , Infección IrruptivaRESUMEN
OBJECTIVES: This study aims to identify COVID-19 breakthrough infections among people with HIV (PWH) across different phases of the pandemic and explore whether differential immune dysfunctions are associated with breakthrough infections. DESIGN AND METHODS: This retrospective population-based cohort study used data from an integrated electronic health record (EHR) database in South Carolina (SC). Breakthrough infection was defined as the first COVID-19 diagnosis documented in the state agency after the date an individual was fully vaccinated (ie, 2 doses of Pfizer/BNT162b2 or Moderna/mRNA-1273, or 1 dose of Janssen/Ad26.COV2.S) through June 14, 2022. We analyzed the risk and associated factors of the outcome using Cox proportional hazards models. RESULTS: Among 7596 fully vaccinated PWH, the overall rate of breakthrough infections was 118.95 cases per 1000 person-years. When compared with the alpha-dominant period, the breakthrough infection rate was higher during both delta-dominant (HR: 1.50; 95% CI: 1.25 to 1.81) and omicron-dominant (HR: 2.86; 95% CI: 1.73 to 4.73) periods. Individuals who received a booster dose had a lower likelihood of breakthrough infections (HR: 0.19; 95% CI: 0.15 to 0.24). There was no association of breakthrough infections with degree of HIV viral suppression, but a higher CD4 count was significantly associated with fewer breakthroughs among PWH (>500 vs <200 cells/mm3: HR: 0.68; 95% CI: 0.49 to 0.94). CONCLUSIONS: In our PWH population, the incidence of breakthrough infections was high (during both delta-dominant and omicron-dominant periods) and mainly associated with the absence of a booster dose in patients older than 50 years, with comorbidities and low CD4 count.
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COVID-19 , Infecciones por VIH , SARS-CoV-2 , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Masculino , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/complicaciones , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , SARS-CoV-2/inmunología , South Carolina/epidemiología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Estudios de Cohortes , Recuento de Linfocito CD4 , Infección IrruptivaRESUMEN
BACKGROUND: Data on the dynamics and persistence of humoral immunity against SARS-CoV-2 after primary vaccination with two-dose inactivated vaccine (CoronaVac) are limited. This study evaluated the sequential effects of prior infection, heterologous boosting with mRNA-1273 (Moderna), and the occurrence of Omicron vaccine-breakthrough infection (VBI) thereafter. METHODS: We evaluated anti-spike IgG (Abbott) and neutralising (cPASS/GenScript) antibody (nAb) titers up to one year after mRNA-1273 boost in two-dose-CoronaVac-primed Indonesian healthcare workers (August 2021-August 2022). We used linear mixed modeling to estimate the rate of change in antibody levels, and logistic regression to examine associations between antibody levels and VBI. RESULTS: Of 138 participants, 52 (37.7%) had a prior infection and 78 (56.5%) received an mRNA-1273 booster. After two-dose CoronaVac, antibody titers had significantly declined within 180 days, irrespective of prior infection. After mRNA-1273 booster, anti-spike IgG (1.47% decline/day) and Omicron B.1.1.529/BA.2 nAbs declined between day 28-90, and IgG titers plateaued between day 90-360. During the BA.1/BA.2 wave (February-March 2022), 34.6% (27/78) of individuals experienced a VBI (median 181 days after mRNA-1273), although none developed severe illness. VBI was associated with low pre-VBI anti-spike IgG and B.1.1.529/BA.2 nAbs, which were restored post-VBI. CONCLUSIONS: mRNA-1273 booster after two-dose CoronaVac did not prevent BA.1/BA.2 VBI. Periodic vaccine boosters may be warranted against emerging SARS-CoV-2 variants.
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Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infección Irruptiva , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vacuna nCoV-2019 mRNA-1273/inmunología , Vacuna nCoV-2019 mRNA-1273/administración & dosificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Infección Irruptiva/epidemiología , Infección Irruptiva/inmunología , Infección Irruptiva/prevención & control , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Personal de Salud , Inmunoglobulina G/sangre , Indonesia/epidemiología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunación , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificaciónRESUMEN
BACKGROUND: SARS-CoV-2 vaccines are safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. This study was performed to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. METHODS AND FINDINGS: A retrospective clinical cohort study was performed utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. The primary outcome was the incidence and time to the first positive SARS-CoV-2 molecular test in the Omicron predominant era. Multivariable Cox modeling analyses to determine the hazard of SARS-CoV-2 infection were stratified by calendar time (Period 1: January 1 -June 30, 2022; Period 2: July 1 -December 31, 2022) due to violations in the proportional hazards assumption. In total, 133,191 patients were analyzed. During Period 1, having 3+ comorbidities was associated with increased hazard for breakthrough (HR = 1.16 CI 1.08-1.26). During Period 2 of the study, having 2 comorbidities (HR = 1.45 95% CI 1.26-1.67) and having 3+ comorbidities (HR 1.73, 95% CI 1.51-1.97) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in Period 1 of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. CONCLUSIONS: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age plays an important role in breakthrough infection with the highest incidence among young adults, which may be due to age-related behavioral factors. These findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.
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Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/virología , Masculino , Femenino , Persona de Mediana Edad , SARS-CoV-2/inmunología , Incidencia , Factores de Riesgo , Adulto , Estudios Retrospectivos , Vacunas contra la COVID-19/inmunología , Anciano , Chicago/epidemiología , Comorbilidad , Vacunación , Inmunización Secundaria , Adulto Joven , Infección IrruptivaRESUMEN
Patients with long COVID can develop humoral autoimmunity after severe acute SARS-CoV-2 infection. However, whether similar increases in autoantibody responses occur after mild infection and whether vaccination prior to SARS-CoV-2 breakthrough infection can limit autoantibody responses is unknown. In this study, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with rheumatic autoimmune diseases and diabetes in most individuals, regardless of vaccination status prior to infection. However, patients with long COVID and persistent neurologic and fatigue symptoms (neuro-PASC) have substantially higher autoantibody responses than convalescent control subjects at an average of 8 mo postinfection. Furthermore, high titers of systemic lupus erythematosus- and CNS-associated autoantibodies in patients with neuro-PASC are associated with impaired cognitive performance and greater symptom severity. In summary, we found that mild SARS-CoV-2 primary and breakthrough infections can induce persistent humoral autoimmunity in both patients with neuro-PASC and healthy COVID convalescents, suggesting that a reappraisal of mitigation strategies against SARS-CoV-2 is warranted to prevent transmission and potential development of autoimmunity.
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Autoanticuerpos , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/inmunología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Masculino , SARS-CoV-2/inmunología , Femenino , Persona de Mediana Edad , Adulto , Anciano , Autoinmunidad/inmunología , Fatiga/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Infección IrruptivaAsunto(s)
Anticuerpos Antivirales , Infección Irruptiva , COVID-19 , Reacciones Cruzadas , SARS-CoV-2 , Femenino , Humanos , Masculino , Anticuerpos Antivirales/inmunología , Infección Irruptiva/inmunología , Infección Irruptiva/virología , COVID-19/inmunología , COVID-19/virología , Reacciones Cruzadas/inmunología , Memoria Inmunológica , SARS-CoV-2/inmunologíaRESUMEN
BACKGROUND: Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy. METHODS: We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) versus heterologous (mRNA-1273) booster vaccination in 100 BNT162b2-vaccinated infection-naïve individuals enrolled from October 2021. Post hoc analysis was performed to assess the impact of SARS-CoV-2 infection on humoral and cellular immune responses against wild-type SARS-CoV-2 and/or Omicron subvariants. FINDINGS: 93 participants completed the study at day 360. 71% (66/93) of participants reported first SARS-CoV-2 Omicron infection by the end of the study with similar proportions of infections between homologous and heterologous booster groups (72.3% [34/47] vs 69.6% [32/46]; p = 0.82). Mean wildtype SARS-CoV-2 anti-S-RBD antibody level was significantly higher in heterologous booster group compared with homologous group at day 180 (14,588 IU/mL; 95% CI, 10,186-20,893 vs 7447 IU/mL; 4646-11,912; p = 0.025). Participants who experienced breakthrough infections during the Omicron BA.1/2 wave had significantly higher anti-S-RBD antibody levels against wildtype SARS-CoV-2 and antibody neutralisation against BA.1 and pre-emergent BA.5 compared with infection-naïve participants. Regardless of hybrid immunity status, wildtype SARS-CoV-2 anti-S-RBD antibody level declined significantly after six months post-booster or post-SARS-CoV-2 infection. INTERPRETATION: Booster vaccination with mRNA-1273 was associated with significantly higher antibody levels compared with BNT162b2. Antibody responses are narrower and decline faster among uninfected, vaccinated individuals. Boosters may be more effective if administered shortly before infection outbreaks and at least six months after last infection or booster. FUNDING: Singapore NMRC, USFDA, MRC.
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Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Humanos , SARS-CoV-2/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Femenino , Adulto , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Persona de Mediana Edad , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacuna nCoV-2019 mRNA-1273/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Inmunogenicidad Vacunal , Inmunidad Humoral , Vacunación/métodos , Anciano , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto Joven , Infección IrruptivaRESUMEN
OBJECTIVE: To determine the occurrence of breakthrough COVID-19 infections (BIs) in patients with systemic lupus erythematosus (SLE) compared with patients with other rheumatic autoimmune diseases (rAIDs), patients with non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). METHODS: The study was based on data from 7035 fully vaccinated respondents to the online COVAD questionnaire with SLE (N = 852), rAIDs (N = 3098), or nrAIDs (N = 414), and HCs (N = 2671). BI was defined as COVID-19 infection occurring in individuals vaccinated with ≥ 2 doses (or 1 dose of J&J) ≥ 14 days after vaccination and not after 6 months since the last vaccine dose. Data were analysed using linear and logistic regression models. RESULTS: A total of 91/852 (10.7%) SLE patients reported at least one BI. The frequency of BIs in SLE patients was comparable to that among HCs (277/2671; p = 0.847) and patients with nrAID (39/414; p = 0.552) but higher than that among patients with other rAIDs (235/3098; p = 0.005). No demographic factors or treatments were associated with BIs in SLE patients (p ≥ 0.05 for all). Joint pain was more frequent in SLE patients than in HCs (odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.89-6.04; p < 0.001) or nrAID patients (OR: 2.44; 95% CI: 1.04-5.75; p = 0.041). Patient with SLE did not report a higher frequency of hospitalisation or need for advanced treatment for COVID-19 infection compared with disease controls and HCs, respectively. CONCLUSION: COVID-19 vaccination conferred similar protection against COVID-19 infection in terms of frequency and severity in patients with SLE to that reported by healthy individuals.
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Vacunas contra la COVID-19 , COVID-19 , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/epidemiología , Femenino , COVID-19/prevención & control , COVID-19/epidemiología , Masculino , Persona de Mediana Edad , Adulto , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Vacunación , Estudios de Casos y Controles , Anciano , Enfermedades Autoinmunes/epidemiología , Enfermedades Reumáticas/tratamiento farmacológico , Infección IrruptivaRESUMEN
Notwithstanding the wealth of literature on COVID-19, studies focusing on young adults with autoimmune diseases (AD) are lacking. To determine early (within 7 days) and late (after 7 days) anti-SARS-CoV-2 vaccine-related adverse events (AEs), post-vaccine disease flares, COVID-19 severity and breakthrough infections (B-INFs) in young people with rheumatic diseases (RMDs) and non-rheumatic autoimmune diseases (nr-ADs) compared to healthy controls (HC). Data were captured through the international COVID-19 vaccination in autoimmune diseases (COVAD) 1 and 2 questionnaires. Of 20,685 complete responses, we identified 6010 from patients aged 18-35 years (1692 RMD, 400 nrADs, 3918 HC) who received up to 4 vaccine doses. BNT162b2 was the most frequently administered vaccine and prior to vaccination, 7% of people with nrAD were taking immunosuppressants (IS) versus 80% in RMDs. Early mild AEs were more frequent in RMDs (93%) and nr-ADs (92%) compared to HC (85%). The frequency of late mild AEs was < 20% in all groups. Severe AEs were rare. SARS-CoV-2 infection rates were similar across all groups, however, RMD patients reported a single episode of infection more frequently than nrADs and HC, while nrADs reported multiple infections more frequently than RMD. Self-reported disease flares were reported by 10% or RMD and 7% of nrAD patients. Our study reinforces the safety of anti-SARS-CoV-2 vaccine also in young people with ADs, but it also highlights that among young individuals the number and clinical picture of SARS-CoV-2 infections is affected more by the type of AD rather than by coexisting IS therapy.
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Enfermedades Autoinmunes , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Humanos , COVID-19/prevención & control , Adulto Joven , Femenino , Adulto , Masculino , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , Adolescente , SARS-CoV-2/inmunología , Enfermedades Reumáticas/tratamiento farmacológico , Vacuna BNT162/efectos adversos , Vacunación/efectos adversos , Infección IrruptivaRESUMEN
We aimed to characterise vaccine-induced protection against COVID-19 during five waves caused by Variants of Concern (VOCs). This is a nested case-control study of 3,972 HCW primarily vaccinated with CoronaVac (98%) that evaluated symptomatic SARS-CoV-2 breakthrough infections (BI) in almost two-years follow-up until the 3rd Omicron wave. Predictors of protection against SARS-CoV-2 BI were analysed using conditional logistic regression models. We included 1,491 SARS-CoV-2 breakthrough cases, mostly mild, and 2,962 controls. Most participants (90%) had received at least one booster before the onset of the Omicron waves, mainly BNT162b2. A multivariate logistic regression showed that vaccine-induced protection against BI wanes after six months regardless of the number of monovalent booster doses. Additionally, booster dose with BNT162b2 showed a trend for higher protection compared to CoronaVac during the Omicron waves. In conclusion, immunity of monovalent booster doses against SARS-CoV-2 is short-lasting. Individuals previously vaccinated with an inactivated vaccine should receive a BNT162B2 booster dose.
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Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Personal de Salud , Inmunización Secundaria , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Personal de Salud/estadística & datos numéricos , Femenino , Persona de Mediana Edad , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Adulto , Estudios de Casos y Controles , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Vacunación , Anciano , Infección Irruptiva , Vacunas de Productos InactivadosAsunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Anticuerpos Antivirales/inmunología , Infección Irruptiva , COVID-19/inmunología , COVID-19/virología , COVID-19/genética , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genéticaAsunto(s)
Mpox , Vacunación , Humanos , Mpox/epidemiología , Mpox/virología , Mpox/prevención & control , Masculino , Femenino , Persona de Mediana Edad , Adulto , Infección IrruptivaRESUMEN
Background: Vaccine breakthrough SARS-CoV-2 infections are common and of clinical and public health concern. However, little is known about the immunological characteristics of patients hospitalized due to these infections. We aimed to investigate and compare immune cell subpopulations and induced immune responses in vaccinated and non-vaccinated patients hospitalized with severe COVID-19. Methods: A nested case-control study on adults (≥ 18 years) who received at least two doses of a mRNA-COVID-19 vaccine and were hospitalized with SARS-CoV-2 breakthrough infections and severe COVID-19 between January 7, 2021, and February 1, 2022, were eligible for inclusion. Age- and sex-matched non-vaccinated controls were identified. Immunophenotyping was performed using a custom-designed 10-color flow cytometry prefabricated freeze-dried antibody panel (DuraClone, Beckman Coulter (BC), Brea, Calif). TruCulture (Myriad RBM, Austin, USA) was used to assess induced immune response in whole blood, revealing different critical signaling pathways as a proxy for immune function. All samples were obtained within 48 hours of admission. Results: In total, 20 hospitalized patients with severe COVID-19 and a breakthrough SARS-CoV-2 infection were included, ten vaccinated and ten non-vaccinated patients. Vaccinated patients had lower concentrations of CD19 B cells (p = 0.035), naïve CD4 T cells (p = 0.015), a higher proportion of γδ1 T cells (p = 0.019), and higher unstimulated immune cell release of IL-10 (p = 0.015). Conclusion: We observed immunological differences between vaccinated and non-vaccinated patients hospitalized due to severe COVID-19 that indicate that vaccinated patients had lower B cell concentrations, lower concentrations of CD4 naïve T cells, a skewed gamma-delta V1/V2 ratio, and an exaggerated IL-10 response at admission. These results could indicate a suboptimal immune response involved in SARS-CoV-2 breakthrough infections that cause severe COVID-19 in vaccinated adults. However, the sample size was small, and further research is needed to confirm these results.
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Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , Masculino , Femenino , Persona de Mediana Edad , SARS-CoV-2/inmunología , Anciano , Estudios de Casos y Controles , Vacunas contra la COVID-19/inmunología , Adulto , Hospitalización , Vacunación , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Inmunofenotipificación , Infección IrruptivaAsunto(s)
Vacunas contra la COVID-19 , COVID-19 , Disfunción Cognitiva , SARS-CoV-2 , Vacunación , Humanos , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , Disfunción Cognitiva/prevención & control , Disfunción Cognitiva/inmunología , Vacunas contra la COVID-19/inmunología , Infección IrruptivaRESUMEN
The level of neutralizing antibodies required to confer protection against COVID-19 breakthrough infections (BIs) is unclear, and the ability to know the immune status of individuals against the rapidly changing endemic variants is limited. We assessed longitudinal serum anti-RBD antibody levels and neutralizing activities (NTs) against Omicron BA.5 and XBB.1.5 in healthcare workers following the fourth monovalent and fifth bivalent BA.4-5 vaccines. The occurrence of BIs was also followed, and pre-infection antibody levels were compared between patients who developed BI and those who did not. In addition, we collected whole blood samples on the same day as the sera and stored them on filter papers (nos. 545, 590, and 424) for up to two months, then measured their NTs using dried blood spots (DBS) eluates, and compared them with the NTs in paired sera. Pre-infection levels of NTs were lower in patients who developed BI than those who did not, but the anti-RBD antibody levels were not different between them. The NTs below 50 % using 200-fold diluted sera might be one of the indicators of high risk for COVID-19 BI. However, the NTs against XBB.1.5 at 6 months after the fifth dose of bivalent BA.4-5 vaccine were lower than this threshold in almost half of infection-naïve participants. NTs measured using DBS eluates were strongly correlated with those measured using paired sera, but the time and temperature stability varied with the type of filter paper; no. 545 filter paper was found to most suitable for NT evaluation.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Pruebas con Sangre Seca , SARS-CoV-2 , Humanos , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , Pruebas con Sangre Seca/métodos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Femenino , Masculino , Adulto , Persona de Mediana Edad , Personal de Salud , Infección IrruptivaRESUMEN
This longitudinal prospective controlled multicenter study aimed to monitor immunity generated by three exposures caused by breakthrough infections (BTI) after COVID-19-vaccination considering pre-existing cell-mediated immunity to common-corona-viruses (CoV) which may impact cellular reactivity against SARS-CoV-2. Anti-SARS-CoV-2-spike-IgG antibodies (anti-S-IgG) and cellular reactivity against Spike-(S)- and nucleocapsid-(N)-proteins were determined in fully-vaccinated (F) individuals who either experienced BTI (F+BTI) or had booster vaccination (F+Booster) compared to partially vaccinated (P+BTI) and unvaccinated (U) from 1 to 24 weeks post PCR-confirmed infection. High avidity anti-S-IgG were found in F+BTI compared to U, the latter exhibiting increased long-lasting pro-inflammatory cytokines to S-stimulation. CoV was associated with higher cellular reactivity in U, whereas no association was seen in F. The study illustrates the induction of significant S-specific cellular responses in F+BTI building-up basic immunity by three exposures. Only U seem to benefit from pre-existing CoV immunity but demonstrated inflammatory immune responses compared to F+BTI who immunologically benefit from enhanced humoral and cellular immunity after BTI. This study demonstrates that individuals with hybrid immunity from COVID-19-vaccination and BTI acquire a stable humoral and cellular immune response that is maintained for at least 6 months. Our findings corroborate recommendations by health authorities to build on basic immunity by three S-protein exposures.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Celular , Glicoproteína de la Espiga del Coronavirus , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vacuna nCoV-2019 mRNA-1273/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Infección Irruptiva/inmunología , Infección Irruptiva/prevención & control , Proteínas de la Nucleocápside de Coronavirus/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Citocinas/inmunología , Inmunización Secundaria , Inmunoglobulina G/sangre , Estudios Longitudinales , Fosfoproteínas/inmunología , Estudios Prospectivos , Glicoproteína de la Espiga del Coronavirus/inmunología , VacunaciónRESUMEN
The ZF2001 vaccine has demonstrated high efficacy in preventing coronavirus disease 2019 (COVID-19). However, the clinical characteristics of breakthrough infections in vaccinated individuals and the risk factors for adverse outcomes in COVID-19 patients remain unclear. We conducted a retrospective single-center cohort study at Xiangya Hospital of Central South University, including 210 fully vaccinated COVID-19 inpatients from December 5, 2022, to January 31, 2023. Data on clinical characteristics, laboratory findings, disease severity, treatment, and prognosis were collected and analyzed. Our findings revealed that COVID-19 inpatients still experienced common symptoms at the onset of illness, but most laboratory findings were within the normal range, except for white blood cell count (WBC), lymphocyte count, and lactate dehydrogenase (LDH) levels. Following standard treatment, 95.7% of patients were discharged from the hospital. We identified seven variables significantly associated with a higher risk of adverse outcomes, including age over 65, elevated WBC count, reduced lymphocyte count, higher levels of blood urea nitrogen (BUN), LDH, troponin, D-dimer, and procalcitonin. This study supports the substantial clinical benefits of the ZF2001 vaccine for COVID-19 patients. Additionally, age over 65, elevated WBC count, reduced lymphocyte count, and higher blood levels of BUN, LDH, D-dimer, and procalcitonin may be used as predictive factors for disease progression in fully vaccinated COVID-19 inpatients.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Factores de Riesgo , SARS-CoV-2/inmunología , Adulto , Pacientes Internos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunación , Anciano de 80 o más Años , Infección Irruptiva , Vacunas de SubunidadRESUMEN
BACKGROUND: As of 2024, vaccination remains the main mitigation measure against COVID-19, but there are contradictory results on whether people living with HIV (PLWH) are less protected by vaccines than people living without HIV (PLWoH). In this study we compared the risk of SARS-CoV-2 infection and COVID-19 hospitalisation following full vaccination in PLWH and PLWoH. METHODS: We linked data from the vaccination registry, the COVID-19 surveillance system and from healthcare/pharmacological registries in four Italian regions. We identified PLWH fully vaccinated (14 days post completion of the primary cycle) and matched them at a ratio of 1:4 with PLWoH by week of vaccine administration, age, sex, region of residence and comorbidities. Follow-up started on January 24, 2021, and lasted for a maximum of 234 days. We used the Kaplan-Meier estimator to calculate the cumulative incidence of infection and COVID-19 hospitalisation in both groups, and we compared risks using risk differences and ratios taking PLWoH as the reference group. RESULTS: We matched 42,771 PLWH with 171,084 PLWoH. The overall risk of breakthrough infection was similar in both groups with a rate ratio (RR) of 1.10 (95% confidence interval (CI):0.80-1.53). The absolute difference between groups at the end of the study period was 8.28 events per 10,000 person-days in the PLWH group (95%CI:-18.43-40.29). There was a non-significant increase the risk of COVID-19 hospitalisation among PLWH (RR:1.90; 95%CI:0.93-3.32) which corresponds to 6.73 hospitalisations per 10,000 individuals (95%CI: -0.57 to 14.87 per 10,000). CONCLUSIONS: Our findings suggest PLWH were not at increased risk of breakthrough SARS-CoV-2 infection or COVID-19 hospitalisation following a primary cycle of mRNA vaccination.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Infecciones por VIH , Hospitalización , Humanos , Hospitalización/estadística & datos numéricos , Italia/epidemiología , COVID-19/prevención & control , COVID-19/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Infecciones por VIH/epidemiología , Adulto , Vacunas contra la COVID-19/administración & dosificación , Anciano , SARS-CoV-2 , Sistema de Registros , Adulto Joven , Factores de Riesgo , Vacunación/estadística & datos numéricos , Incidencia , Infección IrruptivaRESUMEN
BACKGROUND: Despite impaired humoral response in patients treated with immunosuppressants (ISPs), recent studies found similar severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection compared to controls. One potential explanation is the rapid generation of humoral response on infection, but evidence is lacking. OBJECTIVES: We investigated the longitudinal dynamics of the SARS-CoV-2 antibody repertoire after SARS-CoV-2 delta and omicron breakthrough infection in patients with immune-mediated inflammatory diseases (IMIDs) receiving ISP therapy and controls. METHODS: As a prospective substudy of the national Target-to-B! (T2B!) consortium, we included IMID patients receiving ISPs therapy and controls who reported SARS-CoV-2 breakthrough infection between July 1, 2021, and April 1, 2022. To get an impression of the dynamics of the antibody repertoire, 3 antibody titers of wild-type RBD, wild-type S, and omicron RBD were measured at 4 time points after SARS-CoV-2 breakthrough infection. RESULTS: We included 302 IMID patients receiving ISPs and 178 controls. Antibody titers increased up to 28 days after breakthrough infection in both groups. However, in IMID patients receiving therapy with anti-CD20 and sphingosine-1 phosphate receptor modulators, antibody titers were considerably lower compared to controls. In the anti-TNF group, we observed slightly lower antibody titers in the early stages and a faster decline of antibodies after infection compared to controls. Breakthrough infections were mostly mild, and hospitalization was required in less than 1% of cases. CONCLUSIONS: Most ISPs do not influence the dynamics of the SARS-CoV-2 antibody repertoire and exhibit a rapid recall response with cross-reactive antibody clones toward new virus variants. However, in patients treated with anti-CD20 therapy or sphingosine-1 phosphate receptor modulators, the dynamics were greatly impaired, and to a lesser extent in those who received anti-TNF. Nevertheless, only a few severe breakthrough cases were reported.
Asunto(s)
Anticuerpos Antivirales , COVID-19 , Inmunidad Humoral , Inmunosupresores , SARS-CoV-2 , Humanos , COVID-19/inmunología , Masculino , SARS-CoV-2/inmunología , Persona de Mediana Edad , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Inmunosupresores/uso terapéutico , Anciano , Estudios Prospectivos , Adulto , Glicoproteína de la Espiga del Coronavirus/inmunología , Infección IrruptivaRESUMEN
Since March 2020, the COVID-19 pandemic has swiftly propagated, triggering a competitive race among medical firms to forge vaccines that thwart the infection. Lebanon initiated its vaccination campaign on February 14, 2021. Despite numerous studies conducted to elucidate the characteristics of immune responses elicited by vaccination, the topic remains unclear. Here, we aimed to track the progression of anti-spike SARS-CoV-2 antibody titers at two-time points (T1: shortly after the second vaccination dose, T2: six months later) within a cohort of 201 adults who received Pfizer-BioNTech (BNT162b2), AstraZeneca, or Sputnik V vaccines in North Lebanon. Blood specimens were obtained from participants, and antibody titers against SARS-CoV-2 were quantified through the Elecsys-Anti-SARS-CoV-2 S assay (Roche Diagnostics, Switzerland). We used univariate analysis and multivariable logistic regression models to predict determinants influencing the decline in immune response and the occurrence of breakthrough infections among vaccinated patients. Among the 201 participants, 141 exhibited unchanging levels of antibody titers between the two sample collections, 55 displayed waning antibody titers, and only five participants demonstrated heightened antibody levels. Notably, age emerged as the sole variable significantly linked to the waning immune response. Moreover, the BNT162b2 vaccine exhibited significantly higher efficacy concerning the occurrence of breakthrough infections when compared with the AstraZeneca vaccine. Overall, our study reflected the immune status of a sample of vaccinated adults in North Lebanon. Further studies on a larger scale are needed at the national level to follow the immune response after vaccination, especially after the addition of the third vaccination dose.