RESUMEN
Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac) at a 28-day interval. Using TMT-based proteomics, we identified 1715 serum and 7342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.
Asunto(s)
COVID-19RESUMEN
Background: The ongoing COVID-19 pandemic has led to the focused application of resources toward developing vaccines to prevent COVID-19. However, the efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with metabolic associated fatty liver disease (MAFLD) are still unknown. We aimed to evaluate the safety, tolerability, seroreactivity, and disease flares after SARS-CoV-2 vaccination in MAFLD patients.Methods: For this prospective observational study, we recruited patients receiving two doses SARS-CoV-2 vaccine (CoronaVac). Neutralizing antibody to the SARS-CoV-2 spike receptor-binding domain and IgG to SARS-COV-2 spike-specific were evaluated on Day 0, Day 28, Day 57, and Day 180. All participants with available data were included in the safety and immunogenicity, and disease flares analyses.Findings: 50 MAFLD patients and 50 healthy controls receiving a 0-28 interval vaccination procedure were enrolled. The seroconversion rates of neutralizing antibodies were 16% in MAFLD group (Log10 Geometric Mean Titers (GMT): median 0·783, IQR: 0·719-0·971) and 32% in non-MAFLD group (0·884, IQR: 0·716-1·027) on day 28, and 82% in MAFLD group (1·206, IQR: 1·053-1·467), 90% of non-MAFLD group (1·360, IQR: 1·130-1·464) on day 57, respectively. However, the neutralizing antibody titer in two groups fell below the seropositivity cut-off value on day 180 (MAFLD group 0.928, IQR: 0·773-1·057 vs. non-MAFLD group 0·907, IQR: 0·810-1·009). There was no significant difference in the overall incidence of adverse reactions after two-dose vaccinations between two groups. Furthermore. disease flares were not found in MAFLD group after two-dose vaccinations. On multivariable analysis, NAFLD fibrosis score was negatively associated with seropositive of neutralizing antibody on 180 days (OR 0·03, 95% CI 0·001-0·58, P = 0·022).Interpretation: Two-dose regimen of CoronaVac vaccination in MAFLD patients was safe and well tolerated. MAFLD patients showed a robust immune response after SARS-COV-2 vaccination, which conferred 82% protection against COVID-19 and vaccination does not affect MAFLD disease status.Clinical Trial Registration Details: This trial had been registered in Chinese ClinicalTrials.gov (ChiCTR2100042717).Funding Information: Project of Key Medical Disciplines of Hangzhou, the Health and Science and Technology Planning Project of Hangzhou municipal Health Commission (No. A20210205).Declaration of Interests: JP Shi reports grants from Project of Key Medical Disciplines of Hangzhou for the Department of infectious & Hepatology. QR Zhu reports grants from the Health and Science and Technology Planning Project of Hangzhou municipal Health Commission, during the conduct of the study. All authors declare no competing interests. Ethics Approval Statement: The study was approved by local Hospital Ethics Committee (2021(E2)-KS-049) and written informed consent was obtained from patients involved before enrolment when data were collected.