key: cord-0922191-8j4xw3vp
authors: Passamonti, Serena Maria; Cannavò, Antonino; Trunzo, Valentina; Caporale, Vittoria; Buonocore, Ruggero; DeFeo, Tullia Maria
title: Solid organ transplantation in the Coronavirus disease 2019 (COVID-19) Era: “The great bet” in the North Italy Transplant program (NITp) area
date: 2020-07-07
journal: Transplant Proc
DOI: 10.1016/j.transproceed.2020.07.001
sha: 8cb9620dc346e30fa90558e5889c5cd2d46f5040
doc_id: 922191
cord_uid: 8j4xw3vp

ABSTRACT INTRODUCTION solid organ transplantation may be considered challenging for waitlist patients during Coronavirus disease 2019 (COVID-19) pandemic. AIM the aim of this study was to investigate COVID-19 incidence and mortality in patients transplanted in the North Italy Transplant program (NITp) area during the outbreak. MATERIALS AND METHODS all consecutive patients transplanted from February 20 to April 3, 2020 (6 weeks) were included in our cohort and followed for at least 4 weeks. Survival analyses were performed. RESULTS one-hundred and twenty-four patients were transplanted with 12 (9.7%) hearts, 4 (3.2%) lungs, 39 (31.4%) livers, 67 (54%) kidneys, 2 (1.6%) combined kidney-pancreas. Recipients’ mean age was 51 years (SD±16.6) and 76/124 (61%) were male. Five (4%) developed COVID-19 after a mean of 13 days (SD±6.7) with a cumulative incidence of 4.0% (CI95%, 0.5-7.5). During the follow-up, 5/124 (4%) recipients died for an overall mortality of 4.3% (CI 95%, 0.6-8.0) of whom only one for COVID-19, for a COVID-19-related mortality of 0.8% (CI95%, 0-6.0). CONCLUSIONS this study showed a low COVID-19 incidence and related-mortality in patients transplanted during the COVID-19 era. Further studies with a longer follow-up are mandatory to confirm the safety of transplant procedures.

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Serena Maria Passamonti, M.D., Ph.D., 1 Antonino Cannavò, M.D., 1 Valentina Trunzo, Ph.D., 1 Vittoria Caporale, Ph.D., 1 Ruggero Buonocore, Ph.D., 1 April 3,  2020 (6 weeks) were included in our cohort and followed for at least 4 weeks. Survival analyses were performed.

RESULTS: one-hundred and twenty-four patients were transplanted with 12 (9.7%) hearts, 4 (3.2%) lungs, 39 (31.4%) livers, 67 (54%) kidneys, 2 (1.6%) combined kidney-pancreas. Recipients' mean age was 51 years (SD±16.6) and 76/124 (61%) were male. Five (4%) developed COVID-19 after a mean of 13 days (SD±6.7) with a cumulative incidence of 4.0% (CI95%, 0. 5-7.5) . During the followup, 5/124 (4%) recipients died for an overall mortality of 4.3% (CI 95%, 0.6-8.0) of whom only one for COVID-19, for a COVID-19-related mortality of 0.8% (CI95%, 0-6.0).

this study showed a low COVID-19 incidence and related-mortality in patients transplanted during the COVID-19 era. Further studies with a longer follow-up are mandatory to confirm the safety of transplant procedures. activities has reduced but continued all over the COVID-19 pandemic 12 . The aim of this study was to investigate COVID-19 (donor-related or hospital related) incidence and mortality in transplanted recipients in the NITp area in the first 6 weeks of COVID-119 Era.

This is a cohort study including all consecutive recipients transplanted in the NITp area from 

Before transplantation, all recipients were tested for COVID RNA with nasopharyngeal swab and excluded if positive. After transplantation, patients were admitted to COVID-19 free ICU or COVID-19 free wards (for kidney recipients) and were re-tested for COVID RNA in case of symptoms or according to local clinical and safety policy. Immunosuppressive therapies were started according to local protocols.

Pre-transplant clinical, demographical and immunological recipients' characteristics were collected, as the transplanted organ functioning. The phone call follow-up was performed by a dedicated coordinating center physician who interacted with clinicians of all Transplant Units recording the presence or not of infected transplanted patients, onset timing, COVID-19 symptoms and infection course.

Donors were classified as standard and no-standard according to the risk of potential transmission of an infective or neoplastic disease based on Centro Nazionale Trapianti (CNT) guidelines. Solid organs were allocated according to emergency criteria or regional rotations according to patients' status.

At the beginning of the COVID19 outbreak, CNT recommended the execution of nasopharyngeal swab or bronchoalveolar lavage (BAL) as alternative in all potential donors to exclude SARS-CoV-2

infection. Subsequently, BAL become mandatory and performed the day of procurement or within 24 hours before the recovery. In all cases the SARS-CoV-2 real-time reverse transcription PCR (RT-PCR) result had to be available before the recovery procedure. In case of SARS-CoV-2 PCR positivity, the donor was declared at unacceptable risk and not used. 13 General and clinical donors' characteristics, chest X-ray/ CT scan, organs allocation and recovery were collected for each donor, as the donor-recipient matching. Organs allocation was classified in prioritized or not prioritized according to recipient's status at the time of transplantation.

The first outcome was the cumulative incidence of COVID-19 in transplanted patients and COVID-19 related mortality. Any donors, recipients and recipients-donors matching variables were evaluated as potential predictor of COVID-19 disease.

Continuous variables were expressed as mean values and standard deviation (SD) and compared by independent t-test and Kruskal-Wallis test where appropriate. Categorical variables were expressed as frequencies and percentage values and compared by X 2 test.

Kaplan-Meier survival analyses were performed to assess cumulative incidence of COVID-19

infection and of the different categories of clinical manifestations and mortality. Applied survival analysis by Hosmer-Lemeshow-May was used to fit the models where appropriate.

Statistical analyses were performed within SPSS, version 23.0 (IBM Corp., Armonk, NY). from transplantation, with a cumulative incidence of 4.0% (CI95%, 0.5-7.5) (Figure 1 ). They No differences were found in donors' and recipients characteristics comparing COVID19-positive and negative recipients (Table 3) .

During follow-up, 5/124 (4.0%) recipients died, one of COVID-19, with an overall mortality of 4.3%

(CI 95%, 0.6-8.0) and a COVID-19 related-mortality of 0.8% (CI95%, 0-6.0) (Figure 2 ).

In our study COVID-19 had a 4.0 % incidence in recipients transplanted during the pandemic, with a specific COVID-19-related mortality of 0.8. Patients who developed COVID-19 were all more than 50 years old, transplanted in Lombardy and mainly male. Pre-transplant immunological status seemed to have no influence in the infection onset. Not surprisingly, 2/5 (40%) patients were transplanted and in the most highly affected province in Italy.

We found a lower rate of COVID-19 compared to recently published papers, where patients transplanted before the outbreak and/or on waitlist were included. [9] [10] [11] This difference could be In addition, general characteristics of transplanted patients developing COVID-19 did not differ from COVID-19 positive general population, 4 supporting the hypothesis that transplant per se seemed to be not a risk-factor for the infection.

Some limitations need to be addressed. The main one is the short and variable follow-up to assess the actual incidence of post-transplant SARS-CoV-2 infection. However, all transplanted patients were followed for at least 4 weeks and that period seems to be reasonably long enough to be confident in excluding a donor-related transmission. Due to the low incidence of COVID-19, this study has not enough power to find any correlation between recipients/donors' characteristics and COVID-19 positivity, although this is at our knowlege the first study on patients transplanted in the "COVID-19 Era". As donation is still challenging during the "COVID-19 Era" and limited in number,

we chose to include all consecutive transplanted recipients from different transplant unit afferent to our coordinating center. This may result in possible selection bias from different immunosuppressive therapy, treatment protocols and monitoring but our study was aimed to give a complete picture of real-life. Data were all collected by call survey. We were confident that we have not lost any new COVID-19 diagnosis given the attention to this infection.

In conclusion, among transplanted patients in the "COVID-19 Era", the incidence of infection and its mortality is very low. Considering that transplant is the treatment of choice for several endstage diseases, this infective risk may be considered acceptable due to the real benefit of transplant procedure for the health and quality of life of patients waiting for a solid organ. Further studies with a longer follow-up are mandatory to confirm the safety of transplant procedures. Figure 2A reported the overall mortality. Figure 2B reported COVID-19 related mortality. 

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Coronavirus disease 2019: Implications of emerging infections for transplantation

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The impact of COVID-19 on solid organ donation: The North Italy Transplantation program (NITp) experience. Accepted for publication by Transplantation Proceedings