A recent case report published in the American Journal of Transplantation detailed the recovery of an immunosuppressed transplant recipient from COVID-19. This article provides an overview of the case report with comments from its senior author.
These early findings are of considerable importance since individuals with a compromised immune system are likely more susceptible to poor outcomes from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes the coronavirus disease (COVID-19).
Since recipients of solid organ transplants require long-term immunosuppression to avoid graft rejection by the immune system, this patient population could be hit hard by the pandemic, and optimizing a treatment strategy for transplant recipients and immunosuppressed patients in general is essential for mitigating the loss of life.
- Why could the treatment of COVID-19 be more complicated for transplant recipients?
- Recovery of Kidney Transplant Recipient from COVID-19
- What was the treatment strategy?
- Take-Home Message from Dr. Gang Chen
Why could the treatment of COVID-19 be more complicated for transplant recipients?
The treatment of transplant recipients infected by the coronavirus poses a considerable challenge, since the activity of the immune system in these patients must be rapidly increased to a level sufficient to fight off the virus while limited enough to avoid acute rejection of the transplanted organ by the immune system.
The proper balance of augmentation and suppression of the immune system, a “Goldilocks effect”, must be quickly achieved by the treating medical team. If the immune system of the patient is overly compromised, poor outcomes from infection by the coronavirus could result. A robust yet uncontrolled immune response could save the patient from infection but lead to graft rejection and life-threatening complications.
According to the American Society of Transplantation (AST), available data suggest that transplant recipients receiving immunosuppressive medications may be more likely to progress to pneumonia following SARS-CoV-2 infection, and in addition, may have a higher viral burden and therefore be more infectious than the general population.
An April 2020 publication in the New England Journal of Medicine describing the outcomes of adult transplant recipients diagnosed with COVID-19 found “more rapid clinical progression” of the infection in transplant recipients than among the general population and “a very high early mortality among kidney-transplant recipients with COVID-19.”
While 28% of the transplant patients in the study’s cohort had passed away within three weeks due to infection by the virus, within a similar period of time, the virus has been estimated to lead to the mortality of only 1-5% of individuals in the general population and 8-15% of those older than 70.
The authors stated that their findings “indirectly support the need to decrease doses of immunosuppressive agents in patients with COVID-19.”
Recovery of Kidney Transplant Recipient from COVID-19
According to a recent case report published in the American Journal of Transplantation, a 52-year-old kidney transplant recipient has successfully recovered from SARS-CoV-2 infection, overcoming double pneumonia and other clinical features of the disease course. The report, which provided insight into navigating the complexities of treating a patient with a compromised immune system, was authored by a group from the Institute of Organ Transplantation at the Tongji Medical College of the Huazhong University of Science and Technology in Wuhan, China.
Regarding the insights that the publication may provide to the field of transplantation, senior author and Professor of Surgery Dr. Gang Chen, MD, PhD, told ImmunoFrontiers, “The clinical manifestations of COVID-19 infection in immunosuppressed transplant recipients may be distinctive and treatment methods for COVID-19 pneumonia require careful consideration. In our paper, we reported a typical case of COVID-19 pneumonia following kidney transplantation.”
Dr. Chen continued, “The overall clinical characteristics were similar to those of other non-transplanted adult patients with COVID-19 pneumonia. The patient recovered smoothly after treatment with immunosuppressant reduction coupled with low dose methylprednisolone-based therapy. This case report provides a reference case for treating such patients.”
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What was the treatment strategy?
Prior to contracting the coronavirus, the transplant recipient had received triple maintenance therapy with the immunosuppressive medications prednisone, mycophenolate mofetil (MMF), and tacrolimus for 12 years following transplantation.
After presenting to the hospital with chest tightness, fatigue, fever, and other symptoms, the use of these immunosuppressive agents was discontinued and the patient was treated with intravenous immunoglobulin (IVIG), the corticosteroid methylprednisolone, the antibiotic biapenem, the proton pump inhibitor pantoprazole, and the immune-stimulating cytokine interferon alpha.
By day 16 of illness and day 9 of admission to the hospital, the patient’s clinical features had improved greatly. Two days later, the medical team began to administer tacrolimus and MMF to the patient at the same dosages as prior to the episode of coronavirus infection.
According to the authors, the use of immunosuppressive methylprednisolone during the coronavirus disease course may have not only prevented acute rejection of the transplanted kidney, but also limited the build-up of fluid in the alveoli of the lungs and debilitating symptoms of infection such as fever and fatigue.
While the treatment regimen proved successful for the transplant recipient and may shed light on the approach to treating future immunosuppressed patients suffering from infection by the coronavirus, the authors noted that a “single successfully treated case cannot define effective therapy” and that the treatments used “may or may not have been helpful,” noting the difficulty of “extrapolat[ing] from this patient to recommendations for the transplant population.”
Although multiple therapies for COVID-19 are being evaluated in the clinic, their efficacy is not yet proven, and current treatment focuses on supportive care. Multiple groups have begun developing a vaccine for SARS-CoV-2 including Pennsylvania-based Inovio Pharmaceuticals, and pharmacologic agents such as remdesivir, hydroxychloroquine, and the antiretroviral drug lopinavir/ritonavir are also being investigated.
Notably, the AST has indicated that the management of transplant recipients with COVID-19 must consider the relevance of drug-drug interactions between potential anti-viral treatments and immunosuppressive medications. By inhibiting the liver enzyme CYP34A, which normally metabolizes calcineurin and mTOR inhibits, the HIV drug lopinavir/ritonavir can greatly increase the levels of these immunosuppressive medications.
Take-Home Message from Dr. Gang Chen
Dr. Chen had an important take-home message for readers. “COVID-19 pneumonia in immunosuppressed renal transplant recipients can achieve a good prognosis after appropriate treatment. The adjustment of immunosuppressive agents, use of low-dose methylprednisolone, and protection of renal graft function should be important for treating such patients.”
Zhu L, Xu X, Ma K, et al. (2020) Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression. American Journal of Transplantation. DOI: 10.1111/ajt.15869