Supportive Care Is The Mainstay Of Therapy

On December 31, 2019 the Wuhan Health Commission reported clusters of people with pneumonia that were epidemiologically linked to a seafood and live animal market in Wuhan, China.1-3 The etiology was identified as a novel coronavirus, with a presumptive zoonotic origin.2 The virus was recently designated severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and the disease named Coronavirus Disease 2019 (COVID-19).4, 5 While initially it seemed to have limited person-to-person spread, the ability for human-to-human transmission from symptomatic individuals became apparent later in the epidemic.3-7 Whether transmission can occur during the incubation period or from asymptomatic infected individuals is unknown. By mid-February 2020, the COVID-19 had expanded to include over 50 000 confirmed cases, (over 6000 severe), involving 28 countries around the world;4, 5 15 cases have been confirmed in the United States thus far.5 Comorbidities including cardiovascular disease, cerebrovascular disease, and diabetes are present in one third to one half of reported cases and these patients appear to be at greater risk of serious complications.8 Nosocomial spread may have been aided when patients presented with less classic gastrointestinal symptoms, delaying diagnosis and attention to infection prevention precautions.7

To our knowledge, COVID-19 has not been described in organ transplant recipients or donors. However, related viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) were reported in transplant recipients during prior outbreaks of these viruses.9, 10 Kumar et al.9 reported a fatal case of a liver transplant recipient with SARS that infected several other individuals, predominantly healthcare workers, illustrating a “super-spreader” event. AlGhamdi et al10 described MERS-CoV in 2 renal transplant recipients, 1 of whom had no fever and as such did not meet the case definition for MERS-CoV; he was tested based on respiratory distress and epidemiologic knowledge and thereby appropriately diagnosed. Due to the need for immunosuppression in solid organ transplant recipients, they may be anticipated to have more intense and prolonged shedding of virus, thus potentially increasing the risk of transmission to contacts including healthcare workers. While closely related to SARS-CoV and MERS-CoV, the mortality associated with COVID-19 may be lower than what was reported with the previous epidemic novel coronaviruses. However, caution is still required as we do not yet know the full impact of the infection as it spreads to more diverse populations.4, 5, 11

The current COVID-19 epidemic is still in its early stages and while acquisition of knowledge is rapidly accumulating, there are many unknowns for the community at large and the transplant community in particular. Nevertheless, it is imperative that we anticipate the potential impact on the transplant community in order to avert severe consequences of this infection on both the transplant community and contacts of transplant patients. As we learn more about the infection, recommendations may need to change; an essential element of any recommendation is the ability to revise them in real time.

Based on the experiences with previous coronaviruses, we anticipate that an exposed transplant recipient would be infected; however, less is known about the risk of transmission from donor to recipient. The chance of a donor-derived infection may be influenced by donor exposures as well as infectivity of people in the incubation period and of asymptomatic individuals. The degree and duration of viremia and viability of the virus within blood or specific organ compartments would also impact the risk of donor transmission. Attention to donor epidemiological risk factors may help to diminish the risk of donor transmitted infection. The incubation period for COVID-19 is estimated to be 2-14 days.2-8 In a report of 41 patients admitted with confirmed COVID-19, 6 (15%) had RNA detected in plasma.12 RNA has also been detected in stool of an infected individual; thus sites other than the respiratory tract can be affected.13 The implications of these findings remain unclear and as noted by the US Food and Drug Administration (FDA), as of now there have not been reported cases of transfusion-transmitted coronaviruses.14 There is no formal FDA guidance for blood donors; however, it is anticipated that a person with an acute respiratory illness of any kind would be recused from blood donation. Therefore, while offering some reassurance, it does not negate the need for caution with a new coronavirus. In addition, the American Red Cross and European Centre for Disease Prevention and Control (ECDC) recommend a 28-day and 21-day delay, respectively, for donation for individuals with travel to high-risk areas or contact with a person with suspected or proven COVID-19.15, 16 The ECDC recommends 28-day delay after recovery from a confirmed infection.16 Moreover, unlike many donor-derived infections where the risk is largely limited to the recipient, COVID-19 may present a risk to the Organ Procurement Organizations (OPOs) and procurement team; likewise nosocomial spread to other patients and healthcare workers as noted with the 2002 SARS-CoV remains a concern.9

Optimal management strategies have not been determined. Supportive care is the mainstay of therapy. Clinical trials evaluating potential therapies including with remdesivir (an experimental antiviral medicine) and lopinavir/ritonavir are also being conducted.5 Drug-drug interactions of lopinavir/ritonavir with calcineurin inhibitors may limit its use in transplantation.

The emergence of COVID-19 is not the first time the transplant community has had to contend with emerging viruses, nor will it be our last. Consequently, we should learn from past experiences with novel viruses and put safeguards in place for transplant centers and OPOs to protect transplant recipients and healthcare workers in advance of a first case being reported and to mitigate the impact of this epidemic on transplant outcomes.