key: cord-0945572-k4gmdzic
authors: NasrAllah, Mohamed M.; Osman, Noha A.; Elalfy, Mahmoud; Malvezzi, Paolo; Rostaing, Lionel
title: Transplantation in the era of the Covid‐19 pandemic: How should transplant patients and programs be handled?
date: 2020-09-20
journal: Rev Med Virol
DOI: 10.1002/rmv.2149
sha: fb1deb46066442572a26015dcf8d42c977521712
doc_id: 945572
cord_uid: k4gmdzic

Due to the Covid‐19 pandemic caused by SARS‐CoV‐2, transplant programs worldwide have been severely impacted with dwindling numbers of transplantations performed and a complete halt in several areas. In this review we examine whether SARS‐CoV‐2 infection presents differently in transplant recipients, whom and how we should test, how susceptible the transplant population is to overt infection and describe the range of outcomes. From retrieved published reports on SARS‐CoV‐2infections in 389solid organ transplant recipients reported in the literature, the overall mortality rate was 16.7% (n = 65); however for those with mild or moderate Covid‐19 disease this was 2.9% and 2.3% respectively; conversely, for those with severe infection the mortality rate was 52.2%.We then address questions regarding halting transplantation programs during this pandemic, whether all human tissues being considered for transplantation are capable of transmitting the infection, and if we should alter immunosuppressive medications during the pandemic.

Transplantation, considered largely an elective procedure, has lost its priority. The transplant community now eagerly awaits data often obtained under difficult circumstances during the pandemic and associated with the necessity for hasty reporting. These unusual circumstances have meant that results obtained have been derived from case reports, case series, early registry reports, and short-term small cohorts that have been mostly uncontrolled, not meticulously designed and, in many instances, there have been conflicting results that have, in some cases, increased confusion. [1] [2] [3] [4] [5] [6] The purpose of this review of the published literature is to try to critically appraise the data and evidence reported from transplant studies in terms of transplant outcomes and transplantation organization, in order to reconcile differences between these reports and recommendations.

the transplant population, raising the possibility of higher prevalence of asymptomatic disease in this patient population: a speculation that remains hard to prove. [10] [11] [12] [13] This trend reverberates with the less severe forms of infection observed with other coronaviruses in immunocompromised patients. 14 Manifestations of the disease were recently assessed in a systematic review. 15 Based on the figures from various reports and registry data, the frequency of the clinical manifestations in transplant recipients compared to the general population may generally be rounded up as follows 1, [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] : Amongst symptomatic patients, breathlessness occurs at roughly the same frequency (60-80% of transplant patients and non-transplant patients). Cough and fatigue/myalgia may be more common in transplant recipients: roughly 40% and 20%, respectively, compared to around 4-30% and 10%, respectively, in non-transplant patients. Febrile illness is a major concern that is also difficult to define due to heterogeneous reporting. It is also reasonable to test those with unexplained diarrhea, which is common and sometimes the main presentation in this population. 1, 7, 20, 21 Testing techniques in transplant recipients remain the same as the general population and are reviewed elsewhere. 27 Briefly, PCR nucleic acid testing is the current gold standard for diagnosis and its results vary based on sample site for example, a bronchoalveolar, sputum, or nasopharyngeal swab are more liable to be positive than oropharyngeal or salivary samples (sensitivities in the general population of 93-100%, 72-89%, 59-94%, and 33-77%, respectively). Repeat testing improves the predictive value and proper sample handling is crucial. On the other hand, serological tests have a potential of having a role in surveillance or epidemiological screening of exposure; but are of limited diagnostic value and their clinical value is yet to be determined. Not withstanding, at the date of writing this review, most serological tests are still in the process of validation and approval and only a few have received expedited FDA approval that skips the usual rigorous validation and checking procedures. Whether these tests detect antibodies that are neutralizing or predict infectivity still needs to be proven. [27] [28] [29] [30] The main points to consider among transplant recipients are the utility of testing stool samples by PCR when diarrhea is the salient feature 4, 16, 27 and that the interpretation of antibody testing must be cautious given the anticipated delay in the timeline of seroconversion among immunocompromised patients. 14 Table 1 summarizes data from many of the published case reports/series.

Results fromavailable reports are in many instances confusing and/or conflicting, probably because they should have been evaluated within a more epidemiologically based framework. 31 Infection rates and fatality rates are difficult to confirm given that systematic screening has not taken place and that many of the current figures include open cases that have neither died nor recovered yet. 8, 9 In addition, we need to specify our control groups when defining outcomes in transplant recipients. Ideally, we would want all transplant recipients screened for infection and followed for a reasonable period of time for the rates of infection and outcomes (e.g.hospitalization, mortality, graft dysfunction) compared to both: the general population and waitlisted transplant candidates. Because it is impossible to screen all patients, it would be good to at least have smaller comprehensive registries that record all confirmed cases in a particular area and relate them to a denominator, including all recipients and compare to a control group of all waitlisted subjects in that area.

One set of data that is quite comprehensive comesfrom the registry of the Italian Society of Nephrology. They screened 25 063 kidney-transplant patients, and confirmed infection in only 218 (0.87%). Of these, 54 died (i.e. 25% of cases, 0.2% of total screened recipients). This may be compared to two groups of controls: a) a cohort of 30 129 dialysis patients constituting 67% of the dialysis population in Italy, of whom 1056 (3.5%) were infected and 409 died (39% of cases, 1.3% of total); and b) a second control group of 201 505 infected cases in the general population with 14% mortality. 11 Despite the shortcomings of registry data, we can draw some reasonable conclusions: the incidence of confirmed cases (and mortality) among kidney recipients is lower than in dialysis patients. French registry data are also enlightening: of 43 10 The rates of infection amongst transplant recipients in Wuhan (China) have been similarly low compared to the general population. 33 The reason these figures are meaningful is that they have both a comprehensible denominator: the number (or estimation) of total population at potential risk; and a control 8, 9, 31 : non-transplanted patients in the general population or (even more meaningfully) those on the transplant waiting list. are more diligent with lung and intestine grafts, using meticulous clinical exclusion of exposure, chest CT scans (being sensitive in more severe cases) and in most instances PCR testing. It has also been advocated by some to screen and then isolate potential living donors for 3-7 days. [3] [4] [5] 41 There is some uncertainty on how to proceed if a recipient or liv- aninteractive online video meeting is scheduledand facilitated by the secretariat; patient health records (electronic and/or hard copy) are provided. The tele-clinics have a regular planned schedule with pre-specified slots and our physicians are free to attend those clinics from their homes or the hospital premises. Patients who are suspected of having Covid-19 are also initially interviewed by an infectious disease specialist online and, when necessary, admitted to isolation areas dedicated for our patients at our center. The transplantation unit is accessed via Covid-19-free corridors, and entry into the transplantationunit is vigilantly surveyed. We have no intention of modifying our immunosuppression protocols pre-emptively, and will restart our desensitization program based on national-infection trends.

The authors have no competing interest.

Mohamed M. NasrAllah https://orcid.org/0000-0001-5650-3000

Lionel Rostaing https://orcid.org/0000-0002-5130-7286

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