The viral infection may explain why the pig’s heart failed months after transplantation in a revolutionary operation


May 6, 2022

The operation at the University of Maryland was the first time a genetically modified pig was used as an organ donor

University of Maryland School of Medicine

The swine virus may have contributed to the death of the first person to receive a heart transplant from the animal.

David Bennett died in March at the age of 57, two months after a transplant operation. Bennett, who had severe heart failure, was considered too ill to receive a human heart and received the pig’s organ on a compassionate basis. Ten genetic changes were made to the donor pig to prevent rejection of its organ, with four pig genes deleted and six human genes added.

Bennett initially seemed to be doing well, but doctors behind the transplant have now revealed that they tried to treat a swine cytomegalovirus infection in the weeks before his death.

Transplant surgeon Bartley Griffith at the University of Maryland announced the presence of cytomegalovirus in a Talk to the American Transplant Society on April 20. “We’re starting to find out why he left,” he said MIT Technology Review.

MIT Technology Review reports that Griffith says the viral infection may be the cause of the pig’s heart failure, not Bennett’s immune system, which rejects the organ. “There is no evidence that the virus has infected the patient or infected tissues or organs outside the heart,” said a spokesman for the University of Maryland.

Cytomegaloviruses are associated with herpes viruses, which cause herpes and shingles. Once the animals are infected, the viral DNA remains in some cells. Their immune system usually keeps the virus under control, but if the animal is weakened, the virus can reactivate and cause new infections.

Bennett would not be immune to the swine cytomegalovirus, which gave the virus a chance to reactivate and infect the transplanted heart. The virus does not infect human cells, said Joachim Dener of the Free University of Berlin in Germany. Bennett is also on immunosuppressive drugs that may have prevented his immune system from responding fully.

The virus was first detected in blood taken 20 days after Bennett’s transplant. The team has tried a variety of treatments, including a drug used to treat human cytomegalovirus infections called cidofovir, and Bennett appears to be recovering from a rapid deterioration in his condition. When Bennett’s immune system began to react to the virus, it may have triggered an inflammatory response known as a cytokine storm that damages the heart, Griffith said.

In 2020, Denner and his colleagues discovered this baboons do not live that long if they develop swine cytomegalovirus infections after pig heart transplants. But no one can say for sure how much the virus contributed to Bennett’s death, Denner said. “He was very, very sick.”

Organ-bred pigs are kept in special, clean facilities so that they are free of pathogens. Failure to detect the virus before transplantation may be due to insufficiently sensitive tests, Denner said. He has developed a sensitive tests to detect porcine cytomegaloviruswhich his laboratory used in 2016 detection of the virus in pigs bred for biomedical research. These tests were positive even in samples that were negative when tested by laboratories in the United States.

“The testing mentioned by the researcher in your article is experimental [and] it was not available to our surgical surgeons during this transplant, ”said a Maryland spokesman when asked if these tests were used by Griffith’s team.

Detecting latent infections – where viral DNA is found in several cells and no viruses are produced – is more difficult than identifying active infections, but can be done in two ways. The first is to look for viral DNA in blood or tissue samples. The second is to look for antibodies against the virus. Denner’s lab uses both methods. It is not clear which tests were performed before Bennett’s transplant.

“The healthy donor pig used for xenotransplantation has been tested for pathogens repeatedly. He was tested just before being sent to Maryland and just before the transplant a few days later. The testing followed protocols adopted by the US Food and Drug Administration (FDA). As plans for future clinical trials progress, more sophisticated testing techniques are being developed and validated to ensure that the virus does not go unnoticed, ”said the Maryland spokesman.

If the virus contributed to Bennett’s death instead of because his immune system rejected the organ, Denner’s Baboon study suggests that other transplant recipients may live longer if given hearts without viruses. It can be ensured that the pigs are free of swine cytomegalovirus by weaning the animals 24 hours after birthsays Denner.

Revivicor, a subsidiary of United Therapeutics, developed the pig behind Bennett’s transplant and did not comment on the discovery of the virus. There is no evidence of wrongdoing by companies. No company responded A new scientistrequests for comment before publication.

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