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We read with interest about the prognostic significance of liver function abnormalities in SARS-CoV-2 infection.1 2 Although patients with underlying cirrhosis have an increased risk of death following COVID-19, mRNA vaccine administration is associated with an excellent reduction in mortality.3 4 We aimed to determine the association of the prevalence of the Alpha, Delta and Omicron variants and effectiveness of the BNT162b2 or 1273-mRNA vaccines among participants with cirrhosis.
We performed a test-negative case–control study of participants with cirrhosis in the Veterans Outcomes and Costs Associated with Liver disease cohort, who had a SARS-CoV-2 PCR between 1 February 2021 and 21 January 2022.5–7
Participants with a positive PCR were considered as cases, and others, as controls. Propensity score (PS) matching was used to match cases and controls, with PS of being a case derived from a logistic regression that included the participant’s age group, sex, race/ethnicity, alcohol, body mass index, diabetes, current tobacco use, Alcohol Use Disorders Identification Test-Concise (AUDIT-C) score, cirrhosis comorbidity index, hypertension, chronic obstructive pulmonary disease, Child-Pugh Score, location, baseline lab results (alanine aminotransferase, platelet count, creatinine, total bilirubin, international normalised ratio and Model For End-Stage Liver Disease-Sodium (MELD-Na)) and COVID-19 test month. The proportion of variants in the community was obtained from the weekly Center for Disease Control genomic surveillance data.8 Three periods were defined: alpha predominant period from 1 February 2021 to 25 July 2021, Delta predominant from 26 July 2021 to 24 December 2021, and Omicron predominant from 25 December 2021 until 21 January 2022. The effectiveness of mRNA vaccination in preventing COVID-19 infection was examined through a logistic regression model. The model included a categorical variable indicating the most prevalent variant at the time of infection, interaction between vaccination and the prevalent variant, a binary variable to adjust for the receipt of a third dose, and interaction between vaccination and the number of days from full vaccination. Outcomes included symptomatic, and severe/critical COVID-19, defined using the National Institute of Health severity index.9
Of the 120 952 patients in the cohort, we excluded participants who did not have a SARS-CoV-2 PCR (n=100 766), liver transplant recipients (n=526), those partially vaccinated (n=1549), viral vector vaccine recipients (n=832) and those with prior COVID-19 (n=749). The study sample had 16 530 participants, including 2140 with a positive SARS-CoV-2 PCR (cases), and 14 165 who were SARS-CoV-2 PCR negative (controls). After matching, 2836 participants were retained, with equal numbers of cases and controls.
Vaccine effectiveness against symptomatic COVID-19 during the Alpha period was 82% at 2 months (adjusted OR (aOR) 0.18, 95% CI 0.10 to 0.32), 77% at 4 months (aOR 0.23, 95% CI 0.13 to 0.42) and 71% at 6 months from full vaccination (aOR 0.29, 95% CI 0.16 to 0.56) (table 1 and figure 1). Vaccine effectiveness against symptomatic COVID-19 in the Delta period dropped from 68% at 2 months from vaccination (aOR 0.32, 95% CI 0.23 to 0.44), to 59% at 4 (aOR 0.41, 95% CI 0.32 to 0.52) and 48% at 6 months (aOR 0.52, 95% CI 0.42 to 0.64). Full vaccination was not effective against symptomatic COVID-19 in the Omicron period at 2 (aOR 0.70, 95% CI 0.37 to 1.35), 4 (aOR 0.90, 95% CI 0.50 to 1.62) or 6 months (aOR 1.16, 95% CI 0.67 to 1.99). However, the receipt of a third dose of an mRNA vaccine was associated with a reduced odds of symptomatic COVID-19 (aOR 0.52, 95% CI 0.37 to 0.71).
Vaccine effectiveness against severe/critical COVID-19 during the Alpha period was 72% at 2 months (aOR 0.28, 95% CI 0.11 to 0.72), but not significant at 4 (aOR 0.44, 95% CI 0.17 to 1.16) or 6 months from vaccination (aOR 0.68, 95% CI 0.24 to 1.95). In contrast, vaccination was effective against severe/critical COVID-19 during the Delta surge-75% at 2 months (aOR 0.25, 95% CI 0.14 to 0.43), 62% at 4 (aOR 0.38, 95% CI 0.26 to 0.57) and 40% at 6 months (aOR 0.60, 95% CI 0.44 to 0.82).
Vaccination was highly effective against severe/critical COVID-19 during the Omicron period −84% at 2 (aOR 0.16, 95% CI 0.06 to 0.46), 75% at 4 (aOR 0.25, 95% CI 0.10 to 0.63) and 61% at 6 months (aOR 0.39, 95% CI 0.17 to 0.89). Receipt of the third dose was associated with a reduced odds of severe/critical COVID-19 (aOR 0.54, 95% CI 0.32 to 0.92).
In conclusion, COVID-19 vaccination was highly effective against symptomatic COVID-19 during Alpha, and lowest during the Omicron period. However, vaccine effectiveness against severe/critical COVID-19 was highest during Omicron and lowest during the Delta period. The fading effectiveness of vaccination in patients with cirrhosis argues for additional booster dose of an mRNA vaccine in this population.
Patient consent for publication
This study involves human participants and was approved by Approved by Miami VA Institutional Review Board approval for VOCAL study. IRB waived consent due to minimal risk.
Contributors BVJ and BD had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: JA. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: BVJ, DRB and BD. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: BVJ, DRB, YD and BD. Obtained funding: BVJ and BD. Administrative, technical or material support: All authors Supervision: BVJ and BD.
Funding Services supporting the analysis and interpretation of the data of this research project were generated by the VCU Massey Cancer Center Biostatistics Shared Resource, supported, in part, with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
Disclaimer The authors prepared this work in their personal capacity. The opinions expressed in this article are the author's own and do not reflect the view of the Department of Veterans Affairs or the United States government.
Competing interests BVJ received institutional research support from BMS, Exelixis, Exact Sciences, GSK, Glycotest, Inc, H3B biosciences, Viking therapeutics. DEK received institutional research support from Gilead Sciences, Glycotest, Astra Zeneca, Bayer and Exact Sciences. None of the other authors have personal or financial conflicts of interests to declare in relation to this publication
Provenance and peer review Not commissioned; externally peer reviewed.