The world's first failed pig heart transplant two months after scientists: not rejection, it may be a latent virus

According to Xinhua News Agency, on March 9 this year, the University of Maryland Medical Center (UMMC) released news that the patient who received the world's first swine heart transplant surgery died on the 8th. At that time, the hospital did not disclose the exact cause of death. On Jan. 7, David Bennett, 57, reportedly underwent a heart transplant at the center.

Recently, the surgeon who performed the operation said in an interview with foreign media that the pig heart may have a porcine cytomegalovirus lurking in it, and it evaded multiple virus screenings before transplantation. After the transplant, the virus triggered a "storm" immune response in the patient's body, which eventually led to irreversible diastolic heart failure. The research experts stressed that Bennett showed no signs of rejection or contracting the virus.

The experts' claim once again shows concerns about xenotransplantation, that widespread use of modified animal organs could introduce new pathogens into the human body. Experts also said that detecting the virus in the heart of pigs is not necessarily bad news for xenotransplantation studies. If it is confirmed that the porcine virus does work, this could mean that a virus-free heart xenograft can last longer, and a xenograft can also reduce the risk with stricter virus screening.

Low levels of porcine CMV DNA were found in patients, and the condition worsened after a sharp increase in content

At an April 20 symposium with the American Transplant Society, Dr. Bartley Griffiths, a transplant surgeon and director of the Heart Transplant Program at the University of Maryland Medical Center, described the existence of the swine virus and the team's efforts to overcome the problem, arguing that porcine cytomegalovirus may be a potential cause of Bennett's death.

According to it, 20 days after the heart transplant, a test for the first time showed the presence of porcine CYTOV DNA in Bennett's body, but the levels were so low that Griffiths thought it might have been an experimental measurement error, and the biopsy performed on day 34 did not show signs of a strong immune response.

The surgical team believes that porcine cytomegalovirus may be the potential cause of Bennett's death.

However, on the 40th day after the operation, Bennett's condition suddenly worsened, and the results of subsequent tests showed a sharp rise in viral DNA levels. On day 45, Bennett's health suddenly deteriorated. Doctors treated him with antiviral drugs, but the transplanted heart was filled with fluid, doubled in volume and stopped working, and the hospital confirmed that he could not recover and gave him palliative care.

"We're starting to understand why he died," Griffiths said. "We think that the virus that appears on day 20 may be just a little signal at first and then multiply over time." Viruses can be the trigger for all of this. ”

Griffith said the latent virus entered the patient's body through a "free ride", triggering a "storm" immune response in the patient's body, which eventually led to irreversible diastolic heart failure. He stressed that there is currently no evidence that Bennett is infected with the virus or that his body is showing signs of rejection. The pig heart used in the transplant was reportedly genetically modified, "knocked out" of a gene that causes a human rejection response, and a specific gene to prevent overgrowth of pig heart tissue implanted in humans.

Surgeons at the University of Maryland are ready to transplant pig hearts into the human body.

Dr. Jay Fishman, deputy director of the Transplant Center at Massachusetts General Hospital, said the main problem is not porcine CMV itself, as it is a herpes virus that tends to be species-specific, "and they only replicate in the host associated with it." "But the virus can infect transplanted organs, which in turn can lead to a cascade of systemic reactions that could eventually pose a fatal threat to the human body."

Without the virus, could patients live longer?

Revivicol, a biotech company that cultures and modifies the pig's heart, reportedly declined to comment. At the moment, the company has not issued any public statements about the virus.

Griffiths and his colleagues said the pigs in the clinical trial had been screened for the virus multiple times, but the tests may have detected only the active infected virus, not the latent virus. The virus screening was reportedly performed by a nasal swab, but later the researchers detected the virus in the pig's spleen.

Experts say this pioneering transplant provides information for the field of xenotransplantation.

Experts in the field of xenotransplantation say that future organ transplants will require stricter procedures to screen for viruses. Joachim Denner of the Institute of Virology at the Free University of Berlin has said that latent viruses are difficult to detect. And with better detection, the potential viral infection response can be largely avoided.

Mike Curtis, CEO of eGenesis, another U.S. company that grows transplanted organs, said: "Would Bennett have lived longer without the virus?" In response, some surgeons believe that if it is confirmed that the porcine virus does play a role, it may mean that a virus-free heart xenograft can last longer. Supposedly, the latest gene-edited animal organs could beat continuously for years, supposedly. According to previous German studies, if there is a virus, the pig heart transplanted into the baboon can only survive for a few weeks, while the organ without infection can survive for more than half a year.

Historic organ transplants last 2 months, which does not mean "over"

According to previous reports, Bennett first visited the University of Maryland Medical Center last October, when he had to stay in bed and rely on the extracorporeal life support system, extracorporeal membrane oxygenation (ECMO), to maintain his life. His condition was reportedly unsuitable for routine heart transplant surgery and was also unsuitable for artificial heart pump treatment due to his unstable heartbeat. So he agreed to be the first to experiment with gene-edited pig hearts.

"Die or do a transplant." I want to live. Bennett said the day before the operation. The U.S. Food and Drug Administration (FDA) urgently approved the transplant on the grounds of "compassionate use."

After the successful transplant, the new heart has been performing well without any signs of rejection. Extremely weak due to prolonged bed rest, Bennett has also been receiving rehabilitation. The hospital said his condition began to deteriorate in the days leading up to March 8, and he was treated in palliative care after confirming that he could not recover. "Bennett had heart failure before the organ transplant and he couldn't afford it." Griffith said.

Bennett's son thanked the hospital and doctors on behalf of the family for their care for his father. "They (the hospital) are doing their best to create a promising environment at such a difficult time. When my father recovered from the transplant, we were able to spend precious weeks together. He said in a statement. We hope that this story can be the beginning, not the end, of hope. ”

Although this procedure lasted only two months, this pioneering transplant procedure provides information for the field of xenotransplantation and may hopefully help solve the problem of organ shortages in the human body.

"We gained valuable insights into how genetically modified pig hearts can function properly in the human body while immune system responses can be suppressed," said Dr. Mohammed Maushidin, director of xenotransplantation science at the University of Maryland School of Medicine, who participated in Bennett's care. Griffiths also said that the gene editor's ability to operate in good condition for such a long time shows the potential of this therapy.

Red Star News reporter Ding Wen

Edited by Zhang Xun