Swine virus did not cause death in man with pig heart – 7/6/2023 – Science

Multiple factors led to the death of the first person in the world to receive a genetically modified pig heart transplant. Furthermore, porcine viruses detected in the organ did not spread to other parts of the patient’s body.

The conclusion is contained in a study, published on the 29th in the journal The Lancet, carried out by the medical team responsible for the surgery.

David Bennett, 57, had a heart condition that would have killed him if he didn’t receive a heart transplant. With other chronic illnesses though, he was ineligible for a human heart transplant.

On January 7, 2022, he underwent an eight-hour operation at the University of Maryland Medical Center to receive the pig heart transplant.

The pig heart was genetically modified to include human genes that make the organ more tolerable for our immune system. Other pig genes were deleted to prevent the organ from growing inside the body and other functions.

The team of researchers disclosed in the study the main lessons learned from the first xenotransplantation (name given to the procedure that occurs with organs from other animal species) performed in a patient still alive.

The idea is that the research will help to identify possible flaws and improve the way for new procedures in the future.

Bennett’s cause of death was cardiac arrest two months after the procedure.

When analyzing the transplanted organ, the researchers noticed hardening of the myocardial wall, the muscles that cover the heart, multiple damages to the endothelium (thinner and inner wall of the blood capillaries) and inflammation of the organ, probably a consequence of an exacerbated immune response triggered by possible organ rejection.

As the patient’s health deteriorated, doctors administered intravenous immunoglobulin (IVIG) to try to help recover the weakened immune system. During administration, however, the antibodies may have recognized the organ as an invader and provoked an immune response against the heart tissue itself.

In addition, the genetic analysis of the heart detected the presence of two types of porcine viruses, porcine cytomegalovirus (PCMV) and porcine roseola virus (PRV), but no viral DNA fragments were detected in other organs of the patient, the which rules out that a probable viral infection caused the death.

According to the scientists, it is likely that the viruses, which were dormant in the organ, were released from the heart wall after the exaggerated action of the patient’s immune system. With the so-called inflammatory syndrome, the virus may have caused even more deterioration in the heart wall.

One of the points raised by the authors in the study is that an intravenous immunoglobulin test was not performed before administration to the patient to investigate whether there was a possibility of cross-reaction. This exacerbated immune reaction could have been avoided if cells from the pig’s aorta vein had been tested before surgery.

“It is likely that the immune reaction was provoked only after the injection in the patient, since we also detected a decrease in the gene expression of the genes that supposedly prevent rejection and a high expression of genes that regulate the human inflammatory action in the endothelial cells”, explain the authors.

Scientists say, however, that Bennett was “a hero” who volunteered his life for science, and they hope the next patient will be successful. “New genetically modified pig transplants into humans may improve our understanding of xenograft failure mechanisms and help to better manage clinical procedures”, add the authors.