Safety and Immunogenicity of COVID-19 Vaccine Booster in Patients With Liver Diseases (NMCIDCHESS2201)

Safety and Immunogenicity of Third Dose SARS-CoV-2 Vaccine Booster in Patients With Liver Diseases Following Two Doses of Inactivated Vaccines (NMCID-CHESS 2201): a Multicenter Cohort Study

Previous studies should that patients with chronic liver diseases, cirrhosis, hepatocellular carcinoma and post-liver-trasplant status had lower immunological response to SARS-CoV-2 vaccines than healthy population. Along with the waning of antibody and emerging SARS-CoV-2 variants, a third dose SARS-CoV-2 booster vaccination is now considered as an effective strategy. Previous studies showed good safety and immunogenicity of the SARS-CoV-2 booster vaccination in healthy population. However, the relevant information in patients with liver diseases need further research. This study (NMCID-CHESS 2201) aimed to investigate the safety and immunogenicity of the SARS-CoV-2 booster vaccination in population with chronic liver diseases

Study Overview

• Status: Recruiting
• Conditions: Liver Diseases; COVID-19; Vaccine Reaction

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Jingwen Ai; Phone Number: 1376499080; Email: jingwenai1990@126.com
• Study Contact Backup: Name: Qiran Zhang; Phone Number: +8618817875704; Email: qrzhang12@163.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Chongqing Medical University
      • Contact: Li Zhong
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • Recruiting
      • The First Hospital of Lanzhou University
      • Contact: Liting Zhang, MD
      • Contact: Xiaolong Qi, Professor
  • Hebei
    • Baoding, Hebei, China
      • Not yet recruiting
      • Baoding People's Hospital
      • Contact: Wei Qin
  • Heibei
    • Xingtai, Heibei, China
      • Recruiting
      • Xingtai People's Hospital
      • Contact: Dengxiang Liu, Professor
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine
      • Contact: Yanliang Zhang
    • Wuxi, Jiangsu, China
      • Not yet recruiting
      • The Fifth People's Hospital of Wuxi Affiliated Hospital of Jiangnan University
      • Contact: Yuanwang Xiu
    • Zhenjiang, Jiangsu, China
      • Not yet recruiting
      • Zhenjiang Third Hospital Affiliated to Jiangsu University
      • Contact: Shengqiang Zou
  • Liaoning
    • Dalian, Liaoning, China
      • Not yet recruiting
      • The First Affiliated Hospital of Dalian Medical University
      • Contact: Ying Zhu
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • The Sixth Peoples Hospital of Shenyang
      • Contact: Ye Gu
  • Qinghai
    • Xining, Qinghai, China
      • Not yet recruiting
      • The Fourth People's Hospital of Qinghai Province
      • Contact: Hongmei Zu
  • Shandong
    • Qingdao, Shandong, China
      • Not yet recruiting
      • The Affiliated Hospital of Qingdao University
      • Contact: Wei Rao
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Huashan Hospital
      • Contact: Wenhong Zhang, Professor; Phone Number: 13801844344; Email: zhangwenhong@fudan.edu.cn
      • Contact: Qiran Zhang, MD; Phone Number: +8618817875704; Email: qrzhang12@163.com
  • Shanxi
    • Jincheng, Shanxi, China
      • Not yet recruiting
      • Jincheng People's Hospital
      • Contact: Zhiyun Hou
    • Linfen, Shanxi, China
      • Not yet recruiting
      • The Third People's Hospital of Linfen City
      • Contact: Fenxiang Li
    • Taiyuan, Shanxi, China
      • Not yet recruiting
      • The Third People's Hospital of Taiyuan
  • Sichuan
    • Luzhou, Sichuan, China
      • Not yet recruiting
      • The Affiliated Hospital of Southwest Medical University
      • Contact: Qingliang Zhu
  • Tianjin
    • Tianjin, Tianjin, China
      • Not yet recruiting
      • The Third Central Hospital of Tianjin
      • Contact: Huiling Xiang
  • Tibet
    • Lhasa, Tibet, China
      • Not yet recruiting
      • The Third People's Hospital of Tibet Autonomous Region
      • Contact: Xiaosong Yan
  • Zhejiang
    • Lishui, Zhejiang, China
      • Not yet recruiting
      • Lishui People's Hospital
      • Contact: Jiaojian Lv

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Population with liver disease who completed the whole-course COVID-19 vaccination and is going to get booster vaccination.

Description

Inclusion Criteria:

• Previously vaccinated with two doses of SARS-CoV-2 vaccines and planning to get booster vaccination.
• Clinically or pathologically diagnosed with pre-existing liver disease, including: chronic liver diseases, cirrhosis, liver cancer, liver transplant subjects, etc.
• Understanding and willing to comply with the study procedures and provides written informed consent.

Exclusion Criteria:

• Pregnancy or lactation.
• Active or known history of SARS-CoV-2 infection.
• Diseases causing immunosuppressive or immunodeficient status or autoimmune diseases.
• A history of discontinuing anti-HBV agents in recent three months.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of neutralizing antibody serological conversion after the booster vaccination	Neutralizing antibody serological conversion is defined as a change from seronegative at baseline to seropositive or a four-fold titre increase if the participant was seropositive at baseline.	Fourteen to 90 days after the booster vaccine
Number and rate of all solicited and non-solicited adverse events	First 7 days after the booster dose, participants will be required to record and be interviewed for adverse events; from day 8 to day 28 after booster dose, safety data were collected by spontaneous report.	Up to 28 days after booster vaccine injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and rate of abnormal laboratory testing results after the booster vaccination	Abnormal laboratory testing results will be record and grade for severity.	Up to 28 days after after booster vaccine injection
Concentration and titre of neutralizing antibody after booster vaccination	The results will be generated from competitive binding immuoenzymatic capture chemiluminescence immunoassays	Baseline and 14 days, 28 days, 90 days, and 180 days after the booster vaccination

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: LanZhou University; The Affiliated Hospital of Qingdao University; The Second Affiliated Hospital of Chongqing Medical University; Peking University Health Science Center; Xingtai People's Hospital; The First Affiliated Hospital of Dalian Medical University; The Affiliated Hospital Of Southwest Medical University; Lishui Country People's Hospital; The Third People's Hospital of Taiyuan; The Fourth People's Hospital of Qinghai Province; Nanjing University of Chinese Medicine; The Third People's Hospital of Linfen City; Jincheng People's Hospital; The Third Central Hospital of Tianjin; Baoding People's Hospital; The Fifth People's Hospital of Wuxi; The Sixth Peoples Hospital of Shenyang; Zhenjiang Third Hospital; The Third People's Hospital of Tibet Autonomous Region

Publications and helpful links

General Publications

• Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
• Sarin SK, Choudhury A, Lau GK, Zheng MH, Ji D, Abd-Elsalam S, Hwang J, Qi X, Cua IH, Suh JI, Park JG, Putcharoen O, Kaewdech A, Piratvisuth T, Treeprasertsuk S, Park S, Wejnaruemarn S, Payawal DA, Baatarkhuu O, Ahn SH, Yeo CD, Alonzo UR, Chinbayar T, Loho IM, Yokosuka O, Jafri W, Tan S, Soo LI, Tanwandee T, Gani R, Anand L, Esmail ES, Khalaf M, Alam S, Lin CY, Chuang WL, Soin AS, Garg HK, Kalista K, Batsukh B, Purnomo HD, Dara VP, Rathi P, Al Mahtab M, Shukla A, Sharma MK, Omata M; APASL COVID Task Force, APASL COVID Liver Injury Spectrum Study (APCOLIS Study-NCT 04345640). Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study). Hepatol Int. 2020 Sep;14(5):690-700. doi: 10.1007/s12072-020-10072-8. Epub 2020 Jul 4.
• Iavarone M, D'Ambrosio R, Lampertico P; CirCoV study group. Reply to: Correspondence on "High rates of 30-day mortality in patients with cirrhosis and COVID-19". J Hepatol. 2020 Dec;73(6):1570-1571. doi: 10.1016/j.jhep.2020.08.001. Epub 2020 Aug 7. No abstract available.
• Qi X, Wang J, Li X, Wang Z, Liu Y, Yang H, Li X, Shi J, Xiang H, Liu T, Kawada N, Maruyama H, Jiang Z, Wang F, Takehara T, Rockey DC, Sarin SK; COVID-Cirrhosis-CHESS Group. Clinical course of COVID-19 in patients with pre-existing decompensated cirrhosis: initial report from China. Hepatol Int. 2020 Jul;14(4):478-482. doi: 10.1007/s12072-020-10051-z. Epub 2020 May 22.
• Moon AM, Webb GJ, Aloman C, Armstrong MJ, Cargill T, Dhanasekaran R, Genesca J, Gill US, James TW, Jones PD, Marshall A, Mells G, Perumalswami PV, Qi X, Su F, Ufere NN, Barnes E, Barritt AS, Marjot T. High mortality rates for SARS-CoV-2 infection in patients with pre-existing chronic liver disease and cirrhosis: Preliminary results from an international registry. J Hepatol. 2020 Sep;73(3):705-708. doi: 10.1016/j.jhep.2020.05.013. Epub 2020 May 21. No abstract available.
• Qi X, Liu Y, Wang J, Fallowfield JA, Wang J, Li X, Shi J, Pan H, Zou S, Zhang H, Chen Z, Li F, Luo Y, Mei M, Liu H, Wang Z, Li J, Yang H, Xiang H, Li X, Liu T, Zheng MH, Liu C, Huang Y, Xu D, Li X, Kang N, He Q, Gu Y, Zhang G, Shao C, Liu D, Zhang L, Li X, Kawada N, Jiang Z, Wang F, Xiong B, Takehara T, Rockey DC; COVID-Cirrhosis-CHESS Group. Clinical course and risk factors for mortality of COVID-19 patients with pre-existing cirrhosis: a multicentre cohort study. Gut. 2021 Feb;70(2):433-436. doi: 10.1136/gutjnl-2020-321666. Epub 2020 May 20. No abstract available.
• He Q, Zhang G, Gu Y, Wang J, Tang Q, Jiang Z, Shao C, Zhang H, Chen Z, Ma B, Liu D, Xie G, Xu D, Huang Y, Zhang H, Liang M, Huang H, Wang Y, Liu H, Yang J, Pan H, Zou S, Li F, Wang F, Liu C, Wang W, Xiong B, Li X, Liu L, Yang J, Qi X. Clinical Characteristics of COVID-19 Patients With Pre-existing Hepatitis B Virus Infection: A Multicenter Report. Am J Gastroenterol. 2021 Feb 1;116(2):420-421. doi: 10.14309/ajg.0000000000000924. No abstract available.
• Ai J, Wang J, Liu D, Xiang H, Guo Y, Lv J, Zhang Q, Li J, Zhang X, Li Q, Liang J, Guo X, Feng Y, Liu L, Zhang X, Qin W, Wang X, Rao W, Zhang Q, Tian Q, Zhang Y, Xie F, Jiang S, Yan Y, Qiu Y, Wu H, Hou Z, Zhang N, Zhang A, Ji J, Yang J, Huang J, Zhao Z, Gu Y, Bian L, Zhang Z, Zou S, Ji H, Ge G, Du X, Hou A, Zhu Y, Cong Q, Xu J, Zu H, Wang Y, Yan Z, Yan X, BianBa Y, Ci Q, Zhang L, Yang S, Gao X, Zhong L, He S, Liu C, Huang Y, Liu Y, Xu D, Zhu Q, Xu X, Lv M, Zhang W, Qi X. Safety and Immunogenicity of SARS-CoV-2 Vaccines in Patients With Chronic Liver Diseases (CHESS-NMCID 2101): A Multicenter Study. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1516-1524.e2. doi: 10.1016/j.cgh.2021.12.022. Epub 2021 Dec 20.
• Rabinowich L, Grupper A, Baruch R, Ben-Yehoyada M, Halperin T, Turner D, Katchman E, Levi S, Houri I, Lubezky N, Shibolet O, Katchman H. Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients. J Hepatol. 2021 Aug;75(2):435-438. doi: 10.1016/j.jhep.2021.04.020. Epub 2021 Apr 21.
• Wang J, Hou Z, Liu J, Gu Y, Wu Y, Chen Z, Ji J, Diao S, Qiu Y, Zou S, Zhang A, Zhang N, Wang F, Li X, Wang Y, Liu X, Lv C, Chen S, Liu D, Ji X, Liu C, Ren T, Sun J, Zhao Z, Wu F, Li F, Wang R, Yan Y, Zhang S, Ge G, Shao J, Yang S, Liu C, Huang Y, Xu D, Li X, Ai J, He Q, Zheng MH, Zhang L, Xie Q, Rockey DC, Fallowfield JA, Zhang W, Qi X. Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study. J Hepatol. 2021 Aug;75(2):439-441. doi: 10.1016/j.jhep.2021.04.026. Epub 2021 Apr 24.
• Ai J, Zhang H, Zhang Q, Zhang Y, Lin K, Fu Z, Song J, Zhao Y, Fan M, Wang H, Qiu C, Zhou Y, Zhang W. Recombinant protein subunit vaccine booster following two-dose inactivated vaccines dramatically enhanced anti-RBD responses and neutralizing titers against SARS-CoV-2 and Variants of Concern. Cell Res. 2022 Jan;32(1):103-106. doi: 10.1038/s41422-021-00590-x. Epub 2021 Nov 23. No abstract available.
• Cornberg M, Buti M, Eberhardt CS, Grossi PA, Shouval D. EASL position paper on the use of COVID-19 vaccines in patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients. J Hepatol. 2021 Apr;74(4):944-951. doi: 10.1016/j.jhep.2021.01.032. Epub 2021 Feb 6.
• Hillus D, Schwarz T, Tober-Lau P, Vanshylla K, Hastor H, Thibeault C, Jentzsch S, Helbig ET, Lippert LJ, Tscheak P, Schmidt ML, Riege J, Solarek A, von Kalle C, Dang-Heine C, Gruell H, Kopankiewicz P, Suttorp N, Drosten C, Bias H, Seybold J; EICOV/COVIM Study Group; Klein F, Kurth F, Corman VM, Sander LE. Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study. Lancet Respir Med. 2021 Nov;9(11):1255-1265. doi: 10.1016/S2213-2600(21)00357-X. Epub 2021 Aug 13.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 10, 2022
• Primary Completion (ANTICIPATED): August 20, 2022
• Study Completion (ANTICIPATED): December 20, 2022

Study Registration Dates

• First Submitted: January 20, 2022
• First Submitted That Met QC Criteria: January 20, 2022
• First Posted (ACTUAL): January 24, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 14, 2022
• Last Update Submitted That Met QC Criteria: February 9, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: safety; immunogenicity; liver diseases; SARS-CoV-2 vaccine booster
• Additional Relevant MeSH Terms: Digestive System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Liver Diseases; COVID-19
• Other Study ID Numbers: CLD-BOOST

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No