key: cord-0710743-uv4gyeji
authors: John, Binu V.; Deng, Yangyang; Dahman, Bassam
title: COVID-19 Vaccination Is Associated with Reduced SARS CoV2 Infection and Death in Liver Transplant Recipients
date: 2022-04-08
journal: Gastroenterology
DOI: 10.1053/j.gastro.2022.04.003
sha: b5d2e4a9c880abd7dad1a807f6c829f48864a94d
doc_id: 710743
cord_uid: uv4gyeji

nan

We thank Drs Tanaka and Vander Weg for their interest in our research exploring COVID-19 vaccination in liver transplant recipients. 1 They discuss several excellent points and clarifications on the methodology, and we appreciate the opportunity to respond.

We chose not to adjust for the etiology of the liver disease that led to transplantation.

The commonest indication for liver transplantation in the VA during the study period were alcohol and chronic hepatitis C related cirrhosis, both of which are uncommon causes of significant liver disease after transplantation. 2,3 Therefore, we felt that unlike studies of participants with cirrhosis, the condition that led to cirrhosis was not a potential confounder in a study of transplant recipients. 4 The variables we chose to adjust for in our multivariable analysis included those that were used in early studies published on the topic. 5,6 However, we agree that diabetes mellitus, race/ethnicity and the geographic location within the United States are important risk factors for COVID-19. 7 We therefore repeated our analysis by controlling for the suggested variables, including location within the United States (Northeast, Southeast, Midwest, South, Northwest, and Southwest), race/ethnicity, and diabetes mellitus, in estimating the propensity scores. We also controlled for diabetes mellitus and race in the Cox hazard model. Our revised analysis shows that the observed associations are similar to the original analysis, with full COVID-19 vaccination associated with a significant reduction in COVID-19 (adjusted Hazard Ratio [aHR] 0.33, 95% CI 0.23-0.49, p<0.0001), symptomatic COVID-19 (aHR 0.32, 95% CI 0.19-0.55, p<0.0001) and COVID-19 related death (aHR 0.11, 95% CI 0.03-0.37, p=0.0001).

Regarding outcomes, we reported the time to a positive PCR test, time to symptomatic COVID-19, and the time to COVID-19 related death. By definition, participants with a positive SARS-CoV-2 PCR (defined as COVID-19) are either symptomatic or asymptomatic, and COVID-19 related death occurs only after being infected with COVID-19. Therefore, we do not consider these as competing events.

We did set different "time-zeros" for the fully vaccinated and controls to match for the time of exposure to COVID-19. We agree that an alternative would be to designate time zero as when vaccines first become available for both groups and treat vaccination status as a time-dependent covariate. However, the number of partially vaccinated participants in our study sample was low, and evaluating the effect of partial vaccination was outside the aims of this study.

We confirm that we applied Cox proportional hazard regression to the pseudopopulation generated through IPTW, adjusted for variables that were believed to be associated with outcomes. As Tanaka et al pointed out, we did not attempt a doubly robust procedure because of the possibility of significant unobserved confounding.

We agree on the importance of addressing confounding and selection bias in observational studies. Propensity score weighting and matching are widely accepted to account for observed characteristics in observational studies. 8, 9 In our study we tried to control for observed covariates that might confound the relation between COVID-19 J o u r n a l P r e -p r o o f vaccination and outcomes. Sensitivity analysis is a great tool to evaluate the size of confounding and bias of some potential confounders that were not observed, and we performed an analysis to estimate the E-value as suggested. We believe that the observed variables we used cover most potential confounders.

Although, factors like psychosocial factors, political beliefs and vaccine hesitancy related to these beliefs may represent unmeasured confounding, it is unlikely that these confounders would significantly change the associations observed, based on the calculated E-values.

All of the above analyses performed revealed consistent associations described in our original estimates, indicating that our analyses are consistent and the findings robust.

J o u r n a l P r e -p r o o f

Coronavirus Disease 2019 Vaccination Is Associated With Reduced Severe Acute Respiratory Syndrome Coronavirus 2

Infection and Death in Liver Transplant Recipients

Evaluation Within 30 Days of Referral for Liver Transplantation is Associated with Reduced Mortality: A Multicenter Analysis of Patients Referred Within the VA Health System

Co-existing Hepatitis C and Alcoholic Liver Disease: A Diminishing Indication for Liver Transplantation?

Association of BNT162b2 mRNA and mRNA-1273 Vaccines With COVID-19 Infection and Hospitalization Among Patients With Cirrhosis

Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients

Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients