Key words : Actual donor, Coronavirus, Potential donor, Transplantation

Introduction

The global public health emergency situation of the COVID-19 outbreak has directly or indirectly impacted all health systems. Unlike previous epidemics such as the Ebola virus, swine flu, and severe acute respiratory syndrome (SARS), which all resulted in significant lethality, COVID-19 has overshadowed various aspects of human life, including health and economic aspects.^1,2

One health service that was negatively affected by COVID-19 was organ transplantation. This negative impact included both recipients and donors. Patients on wait lists for heart, lung, liver, and kidney transplant who do not receive an organ at the proper time can lose the possibility of transplant as the disease progresses and will not be able to use this therapeutic option.³ Also, due to the risks of COVID transmission, there was a failure to refer patients, resulting in a longer wait list, as well as some patients on active wait lists who were not ready for transplant. In cases of marginal organ donors, allocation was challenging.

Even before the COVID-19 pandemic, there has been a wide gap between organ supply and demand, with only 25 of each 1000 patients on wait lists in 2018 having received a solid-organ transplant.⁴ In addition, the rate of death of patients on wait lists was reported as 5% in the United States. It is noteworthy that the US Organ Procurement and Transplantation Network has reported a 50% drop in organ donors,⁵ which has had the greatest impact on lung transplant.

In this regard, Ahmed and colleagues reported a 17% drop in organ supply and an 18% drop in organ transplants over a 90-day period.¹ What makes these changes even more important is the 11% decrease in the rate of consent to organ donation. Factors that influence family decisions are important and require more investigations.⁶ In Spain, according to a study conducted by Domingueaz-Gil and colleagues, organ donations decreased from 7.2 donors to 1.2 donors per day.^7-9 Because of the negative effects of the pandemic on organ transplant, the idea of COVID-light hospitals (which are, as far as possible, COVID-free hospitals) was proposed.

Iran has been one of the most affected countries by COVID 19; thus several rigid criteria have been intended for donor selection¹⁰ and allocation.¹¹ Changes include a focus on donor identification and an increase in the number of calls to detect all potential donors. A system of in-hospital detectors was also introduced for more coverage. With the pandemic, our centers realized that more than 60% of nurses have not participated in organ donation training programs and more than 70% were not aware of their key role in the organ donation process. With the pandemic, it is crucial that management of human resources include determination of learning opportunities. In the present study, we aimed to compare the donation process before and after the COVID-19 pandemic in one organ procurement unit (OPU) in Iran and to discuss different strategies on the donation process during the pandemic.

Materials and Methods

In this cross-sectional study, the aim of the study was to determine the impact of COVID-19 on the organ donation process for donors after brain death. We analyzed all organ transplant-related activities, including the donor identification and selection process, family approach, donors characteristics (sex, age, cause of brain death), number of organs per donor, and types of organs. These factors were compared over 2 intervals: March 2020 to June 2021 (pandemic period) versus November 2018 to February 2020 (pre-pandemic period).

For donor identification, all patients with Glasgow coma score of less than 5 were assessed in 50 hospitals that are under authorization of our OPU. These potential donors were followed daily to determine the final destination and whether brain death criteria were fulfilled; family approach was the next step.

Donor detection process
To identify any potential donors, we use 3 strategies. First, we perform daily contact by telephone with different wards (eg, intensive care units, emergency departments) of 50 hospitals. This involves a sking one assigned person who has been trained on procurement of organs from brain dead donors to identify all patients with Glasgow coma score of less than 5. Identified donors are then followed for more details. Second, we make regular visits at night to detect unidentified potential donors. Third, we prepare a group of nurses who are responsible for informing the OPU about potential donors.

Specific considerations for donor selection during COVID 19
To assess suitable donors, all potential donors must have COVID-19 polymerase chain reaction testing every 48 hours of follow-up until family consent. All donors are required to have at least 1 spiral chest computed tomography scan during hospital admission; potential donors with signs of COVID-19 are excluded. All potential donors with history of the direct contact with known cases of COVID-19 are also excluded.

Family approach and specific considerations for COVID-19
All potential donors should be allocated for recipients before the family is approached. A safe distance with the family is mandatory to protect the family. The time spent for the interview should be limited. Only principal members of the family should take part in the meeting to avoid overcrowding.

Statistical analyses
All data were gathered in Microsoft Excel and analyzed using GraphPad Prism 7. Descriptive data are presented as absolute frequencies and percentages. Continuous variables are reported as means (±SD) or medians (range) and compared using unpaired t tests. A significance level of .05 was used for all analyses, and all P values are reported as 2 tailed.

Results

The number of donors with brain death before and during the COVID-19 pandemic was 218 and 137 with mean age of 42.6 ± 14.5 and 42.8 ± 15.5 years, respectively (P = .82). With regard to age groups, 5% and 4% of donors in the pandemic and pre-pandemic groups, respectively, were under 15 years of age. Among donors in our analyses, 62% and 60.6% of patients in the pandemic and the pre-pandemic groups, respectively, were male (P = 0.43). With regard to marital status, 67.9% and 66.1% of donors in the pandemic and pre-pandemic groups, respectively, were married (P = .73).

With regard to distribution of blood group type, 36.5% and 38.6% of donors with brain death had type O blood and 32.6% and 32.1% had type A blood during and before the pandemic, respectively. No significant difference in blood types between the 2 groups was observed, with blood group distribution similar to that shown in the general population.

Causes of brain death included cranial bleeding in 46.3% of the pre-pandemic group and in 42.3% of the pandemic group. Trauma leading to brain death decreased from 14.6% in the pre-pandemic group to 14.2% in the pandemic group (P = .8). Tumors leading to brain death decreased by more than half during the COVID-19 pandemic (P = .04). Accidents leading to brain death did not differ between the pre-pandemic and pandemic groups. Brain death from toxicity was 7.8% in the pre-pandemic group and 7.3% during the COVID-19 pandemic (not significant).

When we assessed the rate of inappropriate cases of brain death among potential donors, the rate was 3.2% before the pandemic and 3.6% during the pandemic. Moreover, because of our close attention to organ donor selection, after donor selection (step 1 above), the rate of having an unsuitable organ and donation withdrawal decreased from 4.1% to 2.9% in the pandemic period (P = .02). There were some occurrences of a donor candidate having death before donation; in this regard, cardiac death before organ retrieval increased 52% during the COVID-19 pandemic from 25% before to 38% during the pandemic.

Number of organs per donor was 2.3 ± 1.2 and 2.2 ± 1.2 in the 2 intervals with no significant differences (P = .52). During the COVID-19 pandemic, the number of lung procurements in our OPU decreased by 38.4%. Table 1 summarizes the percentages of optimal organs.

The mean number of donors was 9.7 per month in the pre-pandemic group, which decreased to 7.4 at the start of the COVID-19 pandemic. However, despite a fourth wave of COVID-19 in 2021, the mean number of donors per month has steadily increased, reaching to 8.8. The mean number of procured organs per month was 30.3 ± 5.6 before the pandemic, which decreased to 17.5 ± 3.8 in the first year of the COVID-19 outbreak and then gradually rose to 22.2 ± 5.3. The organ donor rate per million population was 14.7 in the pandemic group and 27.4 in the pre-pandemic group in our OPU, which covers a population of 5.5 million in Tehran.

The proportion of actual to potential donors before and during pandemic was 42.16 ± 7.8% and 29.9 ± 4.8%, with a significant difference between groups (Figure 1A). The main reason for this difference was because of unsuitable donors.

During the pandemic, 29.9% of potential donors became actual donors and the rate of unsuitable donors was 38%. Donor loss before getting consent due to poor donor maintenance was 17%, which was a reason for the difference in proportion of actual to potential donors. Another cause was family refusal in 15.1%.

Time to obtain family consent was 21.3 ± 12.3 hours before the pandemic, which significantly increased to 35.1 ± 8.5 hours during the pandemic (P = .008) (Figure 1B).

Discussion

During the COVID-19 pandemic, the approach of surgery only if necessary has had a great impact on organ transplant. Organ transplantation is a specialized field and the only treatment option for patients with vital organ failure. Therefore, funda-mental changes in policies and recommendations of experts over the pandemic were necessary. In Iran and elsewhere, transplant procedures should continue even when elective operations are suspended. In our study, we assessed the consequences of COVID-19 on our organ procurement activities.

In our OPU, donation indexes such as the number of donated organs per donor; the percentage of kidney, liver, heart, and lung donations; and the causes of brain death were almost similar before and during the COVID-19 pandemic. What was affected in our OPU during the pandemic was the time consumed for donor evaluation and family approach. In addition, the high rates of unsuitable donors and donor loss were limitations for organ procurement in our OPU.

Significant decreases in organ transplant have been reported during the COVID-19 pandemic in many countries around the world,^4,8,9 with a 90.6% decrease in France and a 51.1% in the United States. During the lockdown in England, the rate of lung transplant procedures decreased from 66% to 10% during the pandemic and the number of lung transplants decreased from 53 to 12 transplants from March to May 12, 2019, showing a 77% decrease.11 However, many of these collapses later stabilized. In Germany and Slovenia, the COVID-19 pandemic had no significant effect on transplant rates.^12,13 In Iran, lung procurement was affected by the pandemic, although the proportion of optimal lungs was 4.4% (unpublished data). In this regard, Loupy and colleagues stated a relationship between the increase in COVID-19 infections and a reduction in organ transplant surgeries.⁴

In our OPU, we had a 37% decrease in brain dead donors. Reasons for this decrease included a delay in brain death identification due to nursing workload strains during the pandemic and a decrease in the rate of family consent. Indeed, because of circum-stances and regulations for social distancing, face-to-face contact with donor families was replaced by call interviews, which significantly affected family consent. Furthermore, there were concerns with some transplant teams, including insufficient medical staff and insufficient preparation of recipient candidates on wait lists. However, despite all of these limitations, organ transplantation was a priority and was not overlooked.

In Iran, more than 25 000 people are on wait lists for solid-organ transplant.¹⁴ It is noteworthy that some wait lists were updated by delay because patients were not able to have their laboratory tests according to schedules to keep them ready for transplant. Because of this situation, organ allocation criteria need to be revised and new policies should be implemented. In addition, it has been observed that the duration of virus clearance in transplant recipients is longer than in healthy individuals15,16; thus, transplant recipients may be carriers of the virus for medical staff.

In our center, some inflexible criteria for donor selection were considered. To remove any doubt on close contact history of COVID-19, bronchoalveolar lavage tests were mentioned due to their low false negative results.^17-19 In addition, during the pandemic, it was decided that patients with brain death should stay 24 hours longer than usual in the intensive care unit for additional tests and history, thus increasing risk of donor loss.

Another challenge in our OPU was the workload of our organ procurement coordinators who are mostly medical students. Their tasks include visiting COVID-19 patients and COVID-19 vaccinations. Because of these requirements, we trained some students to cover different aspects of the donation process. Family consent rate was influenced by our coordinator ability and varied from 75% to 87%. To address this matter, we considered a chief coordinator to strengthen weak points of each novice coordinator.

Conclusions

COVID-19 has been in Iran since February 2020. Many intensive care units and emergency depart-ments, which are sources of brain death cases, were full of COVID-19 patients. During the first year of the pandemic, organ donation decreased from 14.34 to 7.8 per million population. The actual number of deceased organ donors in our OPU, which covers a population of 5.5 million in Tehran, was reduced by half. However, all transplant centers and OPUs in Iran have made an enormous effort to identify and transplant available organs to reduce the wait list mortality rate despite a higher workload during the pandemic.

References:

1. Ahmed O, Brockmeier D, Lee K, Chapman WC, Doyle MBM. Organ donation during the COVID-19 pandemic. Am J Transplant. 2020;20(11):3081-3088. doi:10.1111/ajt.16199
   CrossRef - PubMed
   
2. Ozbay G, Sariisik M, Ceylan V, Çakmak M. A comparative evaluation between the impact of previous outbreaks and COVID-19 on the tourism industry. Int Hospitality Rev. 2021. doi:10.1108/IHR-05-2020-0015
   CrossRef - PubMed
   
3. Fernandez-Ruiz M, Andres A, Loinaz C, et al. COVID-19 in solid organ transplant recipients: A single-center case series from Spain. Am J Transplant. 2020;20(7):1849-1858. doi:10.1111/ajt.15929
   CrossRef - PubMed
   
4. Loupy A, Aubert O, Reese PP, Bastien O, Bayer F, Jacquelinet C. Organ procurement and transplantation during the COVID-19 pandemic. Lancet. 2020;395(10237):e95-e96. doi:10.1016/S0140-6736(20)31040-0
   CrossRef - PubMed
   
5. Goff RR, Wilk AR, Toll AE, McBride MA, Klassen DK. Navigating the COVID-19 pandemic: initial impacts and responses of the Organ Procurement and Transplantation Network in the United States. Am J Transplant. 2021;21(6):2100-2112. doi:10.1111/ajt.16411
   CrossRef - PubMed
   
6. Kentish-Barnes N, Siminoff LA, Walker W, et al. A narrative review of family members’ experience of organ donation request after brain death in the critical care setting. Intensive Care Med. 2019;45(3):331-342. doi:10.1007/s00134-019-05575-4
   CrossRef - PubMed
   
7. Dominguez-Gil B, Coll E, Fernandez-Ruiz M, et al. COVID-19 in Spain: transplantation in the midst of the pandemic. Am J Transplant. 2020;20(9):2593-2598. doi:10.1111/ajt.15983
   CrossRef - PubMed
8. Michel S, Witt C, Gottlieb J, Aigner C. Impact of COVID-19 on lung transplant Activity in Germany-a cross-sectional survey. Thorac Cardiovasc Surg. 2021;69(1):92-94. doi:10.1055/s-0040-1715436
   CrossRef - PubMed
   
9. Picard C, Le Pavec J, Tissot A; Groupe Transplantation Pulmonaire de la Societe de Pneumologie de Langue Francaise. Impact of the Covid-19 pandemic and lung transplantation program in France. Respir Med Res. 2020;78:100758. doi:10.1016/j.resmer.2020.100758
   CrossRef - PubMed
   
10. Kates OS, Haydel BM, Florman SS, et al. Coronavirus disease 2019 in solid organ transplant: a multicenter cohort study. Clin Infect Dis. 2021;73(11):e4090-e4099. doi:10.1093/cid/ciaa1097.
    CrossRef - PubMed
    
11. Hardman G, Sutcliffe R, Hogg R, et al. Heart transplantation in the UK during the first wave of the SARS-CoV-2 pandemic. Clin Transplant. 2021;35(5):e14261. doi:10.1111/ctr.14261
    CrossRef - PubMed
    
12. Arnol M, Smrkolj T, Avsec D, Gadzijev A, Knezevic I. An increase in kidney transplantation procedures from deceased donors during the COVID-19 epidemic in Slovenia. Transpl Int. 2020;33(11):1562-1564. doi:10.1111/tri.13715
    CrossRef - PubMed
    
13. Qu Z, Oedingen C, Bartling T, Schrem H, Krauth C. Organ procurement and transplantation in Germany during the COVID-19 pandemic. Lancet. 2020;396(10260):1395. doi:10.1016/S0140-6736(20)32213-3
    CrossRef - PubMed
    
14. Iranian Society of Organ Donation. https://www.ehdacenter.ir/fa
    CrossRef - PubMed
    
15. Ogimi C, Greninger AL, Waghmare AA, et al. Prolonged shedding of human coronavirus in hematopoietic cell transplant recipients: risk factors and viral genome evolution. J Infect Dis. 2017;216(2):203-209. doi:10.1093/infdis/jix264
    CrossRef - PubMed
16. Kim SH, Ko JH, Park GE, et al. Atypical presentations of MERS-CoV infection in immunocompromised hosts. J Infect Chemother. 2017;23(11):769-773. doi:10.1016/j.jiac.2017.04.004
    CrossRef - PubMed
    
17. Iwasaki S, Fujisawa S, Nakakubo S, et al. Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva. J Infect. 2020;81(2):e145-e147. doi:10.1016/j.jinf.2020.05.071
    CrossRef - PubMed
    
18. Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020;323(18):1843-1844. doi:10.1001/jama.2020.3786.
    CrossRef - PubMed
    
19. Naghashzadeh, F., Shafaghi, S., Sharif-Kashani, B. et al. Coronavirus disease 2019 outcomes in heart transplant recipients: a single-center case series. J Med Case Rep. 2021;15:453. doi:10.1186/s13256-021-03028-5
    CrossRef - PubMed