Dr. Lilian Lam is a microbiologist, and received her transplant amidst the COVID-19 crisis. Dr. Alin Gragossian received her transplant just over a year ago, and is an emergency medicine resident at the frontlines in the fight against the outbreak.

We are currently living in the midst of a global pandemic. At the end of 2019, a novel coronavirus was linked to a cluster of pneumonia cases in Wuhan, China. Since then, Coronavirus disease 2019 (COVID-19) has quickly spread throughout the world. It is infecting thousands of people globally on a daily basis and has already caused thousands of deaths1-3.

Dr. Lilian Lam is a microbiologist, and received her transplant amidst the COVID-19 crisis. Dr. Alin Gragossian received her transplant just over a year ago, and is an emergency medicine resident at the frontlines in the fight against the outbreak. Knowledge about the virus and best practices to manage the disease are evolving, but little is known about COVID-19 in the context of transplant patients. While most healthy people develop mild symptoms or even remain infectious carriers without symptoms, it is clear that the elderly and those with underlying medical conditions are at higher risk for severe illness with COVID-19.

What does this mean for us in the transplant community?

The people most vulnerable to COVID-19 are the elderly and those that are immunocompromised. The Centers for Disease Control (CDC) have identified organ transplant patients as among the at-risk immunocompromised population4. With a weakened immune system, the body is less able to fight off and recover from infections. Our immune responses become weaker as we age, and others may be immunocompromised due to chronic medical conditions such as diabetes, malnutrition, and other immune disorders. Certain therapies may also weaken the immune system, including those for cancer and transplant patients.

For transplant recipients, it is necessary to take anti-rejection medications called immunosuppressants to prevent the immune system from attacking and damaging the transplanted organ. However, these immunosuppressants also weaken the ability to fight off infections, leaving transplant patients vulnerable to a wide range of viruses, bacteria, and fungi that otherwise do not cause disease in healthy people. At the same time, this may cause symptoms to appear milder due to suppression of the immune system from mounting a strong response. Powerful anti-rejection induction drugs are used at the time of transplant and this is when patients are most severely immunocompromised. This transitions to anti-rejection maintenance drugs for the long-term, lifetime in most contexts, during which patients remain immunocompromised. With a weakened immune system, infection is one of the main hurdles to disease-free survival after transplant.

There is cause for concern that transplant patients are at high-risk for severe complications from COVID-19. Lung infections can quickly become medical emergencies and are a leading cause of death in transplant recipients. We don’t yet know the infectious dose required to cause COVID-19 disease, but for other infections, a lower number of infectious particles and less aggressive strains can cause disease in transplant recipients5. Some infectious agents may also spread further and more quickly than they would inside a healthy person5-6, and there are reports that the novel coronavirus may also invade the central nervous system and gastrointestinal tract7-8. We don’t yet know enough about COVID-19 outcomes in the transplant population, but there are some important cautionary lessons from what we know about other infections.

Finally, major risk factors for COVID-19 fatalities include heart disease, diabetes, lung disease, hypertension, and cancer4. These may also be present in the transplant population, or may arise during recovery from surgery or as unintended effects from treatments. Anti-rejection immunosuppressants increase the likelihood of developing diabetes, hypertension, and cancer– all of which further increase the risk of infection6. Given that transplant patients have a weakened immune system, combined with risk factors for developing severe illness from COVID-19, it is essential to follow guidelines on social distancing and take action to reduce the chances of getting sick.

What do we know about COVID-19 in transplant recipients?

The truth is that we don’t know much yet.

There have been two well-documented cases so far of heart transplant patients with COVID-19 infections9. Both were male heart transplant recipients who were hospitalized in Wuhan, China. One patient had a mild course of infection and was discharged without complications in less than one week. His symptoms were mild—fatigue, nausea, poor appetite—and he had no cough. The second patient was hospitalized for almost one month, required oxygen and aggressive management, but was also discharged without complications.

A descriptive study, also done in China, followed 87 heart transplant recipients from December 2019 – February 2020. They concluded that heart transplant recipients that practiced appropriate prevention measures had a low rate of infection with COVID-19. However, this was all based on early, preliminary data and will need further analysis10.

Lastly, there is a case report of one 52-year-old kidney transplant recipient who successfully recovered from COVID-19 pneumonia a few weeks ago11.

Although promising, all of these reports are based on very few patients. Symptoms, course of hospitalization, and treatment regimens varied in all of these patients. More information is needed regarding complications and COVID-19 infection rates in solid organ transplant recipients.

What can we do as transplant patients and caregivers?

The best way to prevent illness is to avoid being exposed to the virus. This is important for both transplant recipients and those awaiting transplantation. For caregivers, taking precautions to minimize your exposure as well will help keep your loved ones safe.

Lilian is just over a month post-transplant in California, where a state order is in place for people to stay home unless they are going for groceries, pharmacy supplies, or to seek medical attention. She is still being seen in the transplant clinic, but procedures are being postponed when possible. Friends show their support by dropping supplies off at the door and waving from a safe distance away, and they stay connected with virtual movie nights on Netflix Party.

Alin is more than a year post-transplant in Pennsylvania. A state order is also in place for people to stay home unless they are going out for pharmacy supplies or to seek medical attention. Alin’s residency program is encouraging “telemedicine” visits to be performed by any medical professional who is at high-risk for infection or who is quarantined, and they have changed all in-person lecture conferences to virtual conferences. Alin keeps up with her social life via Google Hangouts for now.

Follow public health recommendations in your region and seek the advice of your specific transplant care team.

The following has been recommended by the American Society of Transplantation12:

  • Practice social distancing, particularly because some people may be infected with COVID-19 even though they do not show any symptoms. Stay home as much as possible and postpone non-essential travel.
  • Avoid crowds, put distance between you and others if you must be out.
  • Frequent hand washing and good hygiene.
  • Avoid touching your eyes, mouths, and noses.
  • Ensure you have enough supplies and medication. Consider having medicines mailed to you or having your caregiver pick up your medicines for you.

Lilian Lam completed her PhD in Microbiology & Immunology and MS in Medicine from Stanford University in 2015. As a research fellow at the University of Oxford, she investigates the interactions between microbes and the immune system, and whether these result in health or disease. Currently based in California, she received a heart transplant in February 2020.

Alin Gragossian is currently an Emergency Medicine resident physician at UPMC Pinnacle in Harrisburg, PA. She plans on continuing her medical training in Critical Care Medicine at Mt. Sinai Hospital in New York City this summer. She received an urgent heart transplant at the University of Pennsylvania in January 2019 after a sudden illness.

Resources:

1 World Health Organization https://www.who.int/emergencies/diseases/novel-coronavirus-2019

2 Johns Hopkins University Coronavirus Resource Center https://coronavirus.jhu.edu

3 Centers for Disease Control and Prevention https://www.cdc.gov/coronavirus/2019-ncov/index.html

4 People who are at higher risk for severe illness (COVID-19).

Centers for Disease Control and Prevention. March 22, 2020. https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/people-at-higher-risk.html

5 Fishman JA (2017). Infection in Organ Transplantation. American Journal of Transplantation. https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.14208

6 Fishman JA (2013). Opportunistic Infections– coming to the limits of immunosuppression? Cold Spring Harbor Perspectives in Medicine. https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.14208

7 Li YC, Bai WZ, and Hashikawa T (2020). The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. Journal of Medical Virology. https://doi.org/10.1002/jmv.25728

8 Wu YJ et. al. (2020). Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. The Lancet Gastroenterology & Hepatology. https://doi.org/10.1016/S2468-1253(20)30083-2https://www.myast.org/coronavirus-disease-2019-covid-19-frequently-asked-questions-transplant-candidates-and-recipients

9 Li, Fei et al. “First Cases of COVID-19 in Heart Transplantation From China.” The Journal of Heart and Lung Transplantation. March 2020.

10 Ren, Zong-Li et al. “Epidemiological and Clinical Characteristics of Heart Transplant Recipients During the 2019 Coronavirus in Wuhan, China: A Descriptive Survey Report.” The Journal of Heart and Lung Transplantation. March 2020.

11 Zhu L, Xu X, Ma K, et al. Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression. Am J Transplant. 2020;

12 American Society of Transplantation

https://www.myast.org/coronavirus-disease-2019-covid-19-frequently-asked-questions-transplant-candidates-and-recipients

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