My father had his liver transplant in October 2020 with an absolutely perfect outcome.  He never had any lab abnormalities  indicating rejection, and he took meticulous care of taking his medications, having labs drawn, and touching base with the transplant clinic weekly.  He returned to work about 2.5 months post transplant.  He received his first Moderna vaccine as reported on 3/9/2021 without any side effects.  He received his second Moderna COVID-19 vaccine on 4/6/2021 Given at same location as first Moderna COVID-19 vaccine, Lot number 016B21A on 04/06/2021, RA, IM.  On 5/3/2021, we had a series of text messages about him driving me to a test and nothing was out of order.  On 5/4/2021, he nearly crashed, was severely confused and never recovered from this.  An extremely thorough workup was done (I can obtain these records), his liver function was completely normal, and nobody was able to truly determine a cause for his altered mental status.  He did have 3 very elevated thyroid antibodies, and he was given IV steroids for presumed Hashimoto's Encephalopathy.  Our impression as a family (and I am a (Privacy)) was that he was about 60-75% better on the steroids.  The neurology team did not agree and the IV steroids were stopped with no oral taper.  As he decompensated over the next 4 days, they realized that he was benefitting from steroids and started a long oral taper.  It was somewhat helpful, but really the benefit was questionable.  Prior to the May incident, he had had 1 separate episode of confusion while on a trip in (Privacy).  He also had 2 episodes of bowel incontinence the same day.  This episode occurred 8 days after his 2nd Moderna vaccine (Given at same location as first Moderna COVID-19 vaccine, Lot number 016B21A on 04/06/2021, RA, IM).  The episode was short enough that he was able to drive the 9 hours home from the trip.  As the month and a half long hospitalization ended on 6/18/2021, he had to be moved to assisted living as he was unable to live alone at that point.  After that, things waxed and waned.  His transplant medication had been changed from tacrolimus to sirolimus due to concern that tac could be contributing to altered mental status.  He was doing fine on this and did not have any liver abnormalities.  The lab draw times were inconsistent in assisted living, and I took him once to have accurate labs drawn at a (Privacy) facility.  Ultimately, he was switched to cyclosporine as this could be better monitored given the circumstances.  He was admitted for fluid overload of unknown cause in October 2021.  Liver studies normal.  He did have elevated creatinine so there was a balance of cyclosporine dose and the judicious use of lasix.    In early December 2021, he suddenly became jaundiced, distended abdomen, difficulty breathing and weeping edema in bilateral LE.  His bilirubin was over 12.  He was admitted to (Privacy) where it was determined that he was in severe chronic rejection for which we knew of no cause.  He had 3 liver biopsies.  He had minimal acute rejection and severe chronic rejection with ductopenia and essentially no biliary tracts left.  He failed treatment with IV steroids, IV thymoglobulin, and pheresis combined with IVIG.  While on steroids, he developed a lucid period that lasted for about 2.5 weeks (well beyond steroid discontinuation) with minimal confusion.  This was witnessed by physicians, NPs, PAs, nursing, and family.  His baseline confusion returned around the time he started pheresis treatments.  He did have some notable reduction in inflammation of the liver with normalization of AST and ALT but unfortunately bilirubin did not decrease.  He was treated with pheresis in the event that he had antibody mediated rejection although his biopsy did not indicate that.  It was determined that he truly did have chronic rejection.  During the hospitalization, I was able to speak with a cognitive neurologist at (Privacy) who reviewed his case, including imaging, and went through my dad's story with me.  We discussed that his MRI had not changed from 05/2021 to 10/2021, and as I learned about the chronic rejection, I began to wonder if the working diagnosis of vascular dementia was a red herring.  He did have white matter changes on an MRI as early as 2005, which we do not have possession of.  It is unknown for how long his brain might have looked like this.  His cognitive function did worsen between the 2 most recent MRIs but that the MRI was unchanged was suspect.  The cognitive neurologist felt that if he had some vascular dementia, it would only be stage 2 which would only be associated with mild cognitive impairment.  She felt that the sudden onset and wide swings in his cognitive status were most likely reflective of underlying pathology.  She further felt this way as dementia wouldn't fluctuate in this manner.  She felt that his periods of lucidity were likely his true cognitive baseline.  She felt that if the liver could be improved, there was a good chance that he would just have mild cognitive impairment.  Unfortunately, once he finished pheresis and it failed to reduce bilirubin due to ductopenia, the only option would've been a second transplant, which he did not qualify for because of his cognitive status.  He then developed renal failure without explanation or with the possibility of several different factors.  It was not hepatorenal syndrome, which would be the most expected form of renal failure in a liver transplant patient.  He had acute tubular necrosis.  The only option was dialysis, but based on type of injury, it was unlikely to help and he also would not be able to have a kidney transplant for the same reasons as his liver.  We declined dialysis and he died shortly after of uremia d/t renal failure.  The overall feeling with the destruction of his liver consistent with chronic rejection was that this process had to have begun quite a few months prior.  At a top transplant center with highly skilled professionals, they had never seen rejection not cause lab abnormalities to alert of its presence.  In terms of what might be different about him than patients in the past, we can only point to the fact that he received his first Moderna vaccine roughly around the time the chronic rejection began and his sudden altered mental status that began in early May was likely a symptom and not a cause.  We wonder about the vaccine as potential cause or trigger as it was not tested in transplant patients and it very well could have triggered some form of immune activation.  Of course, we do not know for certain.  We had an autopsy done but the results are not back yet.  My rheumatologist at (Privacy) has also been involved with all things COVID and felt this could be a plausible explanation.  We are all hoping that we might find some answer or cause so that we can help patients like him in the future who have severe cognitive changes without cause and normal liver function after transplant.  We really want to look into this deeply.