A Population-Based Analysis of the Impact of the COVID-19 Pandemic on Solid Organ Transplantation in Ontario, Canada: Policy Response and Changes in Volume and 90-Day Outcomes : Annals of Surgery Open

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Original Study

A Population-Based Analysis of the Impact of the COVID-19 Pandemic on Solid Organ Transplantation in Ontario, Canada

Policy Response and Changes in Volume and 90-Day Outcomes

Gomez, David MD, PhD*,†,‡,§; Stukel, Therese A. PhD‡,§; Baxter, Nancy N. MD, PhD*,‡,§,‖; Acuna, Sergio A. MD, PhD*; Wilton, Andrew S. MSc; Treleaven, Darin MD, MSc¶,#; Ordon, Michael MD, MSc*,†,‡; Kim, S. Joseph MD, PhD, MHS, MBA‡,§,**

Author Information
Annals of Surgery Open 4(1):p e230, March 2023. | DOI: 10.1097/AS9.0000000000000230

Abstract

INTRODUCTION

COVID-19 has caused unprecedented global surgical disruption. Solid organ transplantation (ie, kidney, liver, heart, lung) has not been spared, as a worldwide decrease in transplantation volumes during the first year of the pandemic has been described.1 Decreases in the number of deceased donors due to pandemic lockdowns,2 slowing of living donor transplants due to government-mandated surgical slowdowns, reduced critical care capacity during peak COVID-19 waves, and concerns about safety of transplantation during the pandemic have likely all contributed to decreased transplant activity. To evaluate the impact of the COVID-19 pandemic on solid organ transplantation, we evaluated population-based rates of transplantation during the first 3 waves of COVID-19 in Ontario, Canada, compared with a 3-year pre-COVID-19 baseline period. We then determined if there was a difference in 90-day outcomes after transplantation to evaluate the safety of performing solid organ transplantation during a pandemic.

METHODS

Setting and Study Design

The province of Ontario is Canada’s most populous province with almost 14.6 million inhabitants. All organ procurement and solid organ transplantation activity is coordinated by a central agency, Trillium Gift of Life Network, and is delivered at 1 of 6 transplant centers. Ontario has a universally accessible, single-payer healthcare system.

We conducted a population-based, repeated, cross-sectional study utilizing linked administrative databases held at Institute for Clinical Evaluative Sciences (ICES), which is authorized to collect and use healthcare data for the purposes of health system analysis, evaluation, and decision support. Secure access to these data is governed by policies and procedures that are approved by the Information and Privacy Commissioner of Ontario. Strengthening the Reporting of Observational Studies in Epidemiology reporting guidelines were followed (Appendix 1, https://links.lww.com/AOSO/A199).

Data Sources

The Canadian Institute for Health Information (CIHI) Discharge Abstract Database captures demographic, diagnostic, procedural, and discharge data for all solid organ transplantations and acute care hospitalizations in Ontario. The National Ambulatory Care Reporting System captures similar data for all emergency department (ED) visits in Ontario. The Ontario Laboratories Information System COVID-19 dataset contains all COVID-19 polymerase chain reaction results performed in hospitals and public health laboratories in Ontario. The Registered Persons Database is a vital statistics registry that contains demographic data for all Ontario residents that receive care under the Ontario Health Insurance Plan. Registered Persons Database eligibility files were used to determine population counts and person-weeks at risk. These datasets were deterministically linked using unique encoded identifiers and analyzed at ICES.

Study Population

We identified adult (age 18 years and older) residents of Ontario with valid Ontario Health Insurance Plan numbers who underwent solid organ transplantation (kidney, liver, heart, lung) between January 1, 2017, and July 3, 2021. Procedures were identified using the Canadian Classification of Interventions, which is an alphanumeric coding system designed to capture details on the types of interventions performed (Appendix 2, https://links.lww.com/AOSO/A199). For all solid organ transplant recipients, we ascertained baseline patient demographic characteristics (age, sex, rurality,3 neighborhood income quintile4). All solid organ transplant recipients were followed for outcomes (detailed below) at 90 days post-transplant through October 3, 2021.

COVID-19 Pandemic: Time Periods and Policy Responses

The study period was divided into a pre-COVID-19 baseline period (January 1, 2017–February 29, 2020) and a COVID-19 period. March 1, 2020, defined the start of the “COVID-19 period.” The COVID-19 period was further divided into “wave 1” (March 1, 2020–September 5, 2020), “wave 2” (September 6, 2020–February 27, 2021), and “wave 3” (February 28, 2021–October 3, 2021) based on the nadir in COVID-19 hospitalizations observed between waves in Ontario. We evaluated differences across COVID-19 waves, as the healthcare system experienced differential pressures due to COVID-19 over time.

During wave 1 in Ontario, a triaging system was established in consultation with the medical directors of all transplant centers for solid organ transplantation and organ procurement to reflect regional hospital resource and capacity in the selection of when to proceed with potential donors. Relative activity level ranged from normal (green: usual mix of donors and recipients), to medium (yellow: younger deceased donors, living donor limited to moderately to severely sick recipients), to low (red: only high status, highly sensitized patients) (Appendix 3, https://links.lww.com/AOSO/A199). Movement away from normal activity increasingly restricted selection of older expanded criteria donors (kidney donor profile index >80), donation after circulatory death, and living donors. In April 2020, all transplant centers were placed in a red stage where only the highest-priority transplants (eg, highly sensitized kidney candidates receiving offers from the national Highly Sensitized Patient Program5) were performed, with the exception of lung transplantation, which was placed on hold. All organ procurement and transplantation (deceased and living) restrictions were lifted in July 2020, and no additional mandatory triaging occurred for the rest of the study period.

Finally, public health-mandated slowdowns of all elective surgery in Ontario occurred in wave 1 (March 19, 2020–May 26, 2020)6,7 and wave 3 (April 19, 2021–May 20, 2021). Living organ donation procedures were not specifically restricted under any of the government-mandated slowdowns; however, each hospital was responsible for deciding whether these semi-elective cases would be allowed to proceed during the slowdown periods based on their own COVID-19–related disruptions in critical care and surgical capacity.

Transplant Procedure Volume

Weekly rates of procedures per 1000 persons were generated for each procedure, by age group and sex, using the corresponding population on January 1 of each year as the denominator since it did not change significantly over the year. Rates were generated by organ (kidney, liver, lung, heart) and donor type (deceased vs living), the latter for kidney and liver transplant recipients only.

Data from the pre-COVID-19 baseline period were used to estimate the pre-COVID-19 monthly rate for each type of procedure that would have been predicted during the COVID-19 period had the pandemic not occurred. We utilized similar analytic methods for our work on the severe acute respiratory syndrome pandemic8 and an analysis of the COVID-19 surgical backlog,9 which uses a long baseline period to stabilize the pre-pandemic estimates and control for monthly fluctuations and trends. Poisson generalized estimating equation models for clustered count data were used to model the pre-COVID-19 trend and predict expected COVID-19 period trends. The unit of analysis was the age group-sex-month stratum. The dependent variable was the stratum-specific count to the population in the stratum; the offset was the log of the stratum-specific population. The working correlation structure was autocorrelation with a lag of 1, to account for any monthly surges not accounted for by average month effects. Pre-COVID-19 models included age group-sex interactions, a secular time trend, and pre-COVID-19 month effects to model monthly variations, with April as the reference month. Pre-COVID-19 model coefficients were applied to the post-COVID-19 age-sex-month strata to obtain expected stratum-specific COVID-19 age-sex-month rates and confidence intervals (CIs).

The ratio between the observed monthly procedure rates during the COVID-19 period and the expected rates based on the pre-COVID-19 trends was our primary outcome.8 We computed the expected COVID-19 rates and CIs by applying the linear combination of pre-COVID-19 regression coefficients to the COVID-19 age-sex-month strata and exponentiating these values. The relative change in rates was expressed as the ratio of observed to expected rates (ie, rate ratios [RRs]) by exponentiating the difference of observed and expected COVID-19 log rates and CIs. RRs with procedure volumes below predicted and upper confidence limit below 1.00 mark periods of COVID-19 generated transplant volume deficit while ratios above predicted with lower confidence limit above 1.00 mark periods of transplant volume recovery when compared with what would be expected based on the 3-year baseline period. In order to allow for additional interpretation, RRs were produced for every month of the COVID-19 period, for wave 1, wave 2, wave 3, and for the overall COVID-19 period.

Short-Term Safety

To evaluate whether solid organ transplantation was safely performed during the COVID-19 period versus the pre-COVID-19 baseline period, we ascertained outcomes within 90 days of transplantation. For the initial transplant (ie, index) admission, we evaluated hospital length of stay and in-hospital mortality. In addition, we assessed 90-day outcomes, which included any presentation to the ED, any hospital readmission, retransplantation within 90 days of transplant, transplant nephrectomy within 90 days of transplant, and 90-day mortality. Finally, for those patients who underwent a transplant during the COVID-19 period, we also ascertained whether a diagnosis of COVID-19 was confirmed with a polymerase chain reaction test in Ontario Laboratories Information System COVID-19 within 90 days of transplantation. Short-term safety outcomes were compared between the pre-COVID-19 period, each COVID-19 wave, and the overall COVID-19 period using the χ2 and Kruskal-Wallis nonparametric tests, where appropriate.

RESULTS

A total of 4830 solid organ transplants were performed in Ontario during the study period: 3562 during the historical period (kidney n = 2158, liver n = 720, lung = 508, and heart n = 200) and 1268 during the COVID-19 period (kidney n = 748, liver n = 312, lung = 150, and heart n = 77).

A decrease in the rate of solid organ transplants by 34.4% (RR, 0.656; 95% CI, 0.586–0.734) was observed, with marked reductions during start of wave 1 and the deployment of a provincial triaging system and a trend towards a return to expected volumes by the end of wave 1 (Fig. 1A and Table 1). Transplants again showed a relative decrease in volume by 14.6% in wave 2 (RR, 0.854; 95% CI, 0.770–0.947) and 23.1% in wave 3 (RR, 0.769; 95% CI, 0.690–0.857) despite the triaging system not being activated. Overall, there was a 24.3% relative decrease (RR, 0.757; 95% CI, 0.679–0.844) in solid organ transplants during the COVID-19 period when compared with the expected volume based on the pre-COVID period, which is equivalent to 409 fewer solid organ transplants. Transplant rates were below expected volumes for 14 months, at expected volumes for 1 month, and transplant volume recovery was observed in only 1 out of 16 study months.

TABLE 1. - Relative Change in Observed Versus Expected Transplant Volumes for the COVID-19 Period
Transplant type Wave 1 Wave 2 Wave 3 COVID Period
Overall 0.656 (0.586–0.734) 0.854 (0.770–0.947) 0.769 (0.690–0.857) 0.757 (0.679–0.844)
Heart 0.723 (0.518–1.011) 1.301 (0.846–2.003) 0.690 (0.450–1.059) 0.916 (0.617–1.361)
Lung 0.570 (0.408–0.796) 0.723 (0.552–0.948) 0.714 (0.498–1.025) 0.664 (0.482–0.915)
Liver—living donor 0.799 (0.514–1.242) 1.152 (0.626–2.122) 1.145 (0.670–1.959) 1.022 (0.601–1.738)
Liver—deceased donor 0.888 (0.628–1.254) 0.926 (0.738–1.162) 0.879 (0.573–1.348) 0.899 (0.644–1.256)
Kidney—living donor 0.469 (0.369–0.598) 0.926 (0.722–1.188) 0.631 (0.491–0.811) 0.677 (0.529–0.866)
Kidney—deceased donor 0.679 (0.574–0.804) 0.778 (0.645–0.937) 0.787 (0.645–0.959) 0.743 (0.618–0.892)
Rate ratios with 95% confidence intervals denoting the relative change in observed versus expected transplant volumes for the COVID-19 period (March 1, 2020–July 3, 2021) are shown. Rate ratios with procedure volumes below predicted and upper confidence limit below 1.00 mark periods of COVID-19 generated transplant volume deficit, while ratios above predicted with lower confidence limit above 1.00 mark periods of transplant volume recovery. The COVID-19 period was further divided into a “first wave”: March 1, 2020–September 5, 2020 (blue shaded area), a “second wave”: September 6, 2020–February 27, 2021 (yellow shaded area), and a “third wave”: February 28, 2021–October 3, 2021 (green shaded area) based on the nadir in COVID-19 hospitalizations observed between waves in Ontario.

F1
FIGURE 1.:
Observed and expected rates of solid organ transplantation. Figures show the observed (blue line) and expected rate (red line) of procedures. The expected rate was derived from Poisson generalized estimating equation models for clustered count data. The 3-year pre-COVID-19 baseline period (January 1, 2017–February 27, 2020) and the COVID-19 period (March 1, 2020–July 3, 2021) are shown. The COVID-19 period was further divided into a “first wave”: March 1, 2020–September 5, 2020 (blue shaded area), a “second wave”: September 6, 2020–February 27, 2021 (yellow shaded area), and a “third wave”: February 28, 2021–October 3, 2021 (green shaded area) based on the nadir in COVID-19 hospitalizations observed between waves in Ontario.

Of note, there was a differential impact of COVID-19 based on the type of solid organ transplant. There were no overall differences between the pre-COVID-19 period and the COVID19 period in heart (RR, 0.916; 95% CI, 0.617–1.361, below expected volumes for 6 months, at expected volumes for 6 months, recovery was observed during 4 study months Fig. 1E) or liver transplant rates (RR, 0.934; 95% CI, 0.745–1.171 Fig. 1D), and no difference in living donor liver transplants (RR, 1.022; 95% CI, 0.601–1.738, below expected volumes for 3 months, at expected volumes for 10 months, recovery was observed during 3 study months) or deceased donor liver transplants (RR, 0.899; 95% CI, 0.644–1.256, below expected volumes for 4 months, at expected volumes for 10 months, recovery was observed during 2 study months). However, large and sustained decreases were seen in lung and kidney transplants. Lung transplants decreased by 43% in wave 1 (RR, 0.570; 95% CI, 0.408–0.796), 27.7% in wave 2 (RR, 0.723; 95% CI, 0.552–0.948), and 28.6% in wave 3 (RR, 0.714; 95% CI, 0.498–1.025) (Fig. 1B). Overall, there was a 33.6% decrease (RR, 0.664; 95% CI, 0.482–0.915) in lung transplants during the COVID-19 period when compared with the pre-COVID period, which is equivalent to 77 less lung transplants. Lung transplant rates were below expected volumes for 10 months, at expected volumes for 6 months, and lung transplant volume recovery was not observed in any study month. Similarly, kidney transplants decreased by 38.9% in wave 1 (RR, 0.611; 95% CI, 0.528–0.708), 17% in wave 2 (RR, 0.827; 95% CI, 0.686–0.997), and 26.8% in wave 3 (RR, 0.732; 95% CI, 0.590–0.907). Overall, there was a 27.9% decrease (RR, 0.721; 95% CI, 0.602–0.863) in kidney transplants during the COVID-19 period when compared with the pre-COVID period; equivalent to 294 less kidney transplants (Fig. 1C). The rate of living donor kidney transplants exhibited a larger decrease (RR, 0.677; 95% CI, 0.529–0.866, below expected volumes for 9 months, at expected volumes for 6 months, recovery was observed in only 1 month) when compared with deceased donor kidney transplants (RR, 0.743; 95% CI, 0.618–0.892, below expected volumes for 12 months, at expected volumes for 2 months, recovery was observed in 2 study months), particularly during the first and third waves, coinciding with government-mandated surgical slowdowns. RRs with 95% CI for all transplant types are presented in Table 1 for the overall COVID-19 period and for each COVID-19 wave.

Overall, there were no differences in age, sex, income quintile, or rurality between those transplanted in the pre-COVID-19 period and those transplanted in the COVID-19 period (Table 2). However, demographic changes were observed by organ type and living versus deceased donors. There was a lower proportion of deceased donor kidney recipients aged 60 or over in the first wave, coinciding with province-wide limitations placed on the use of older deceased donors at this time. In contrast, there was a higher proportion of living donor kidney recipients aged 60 or over in wave 3 (Table 2). No other differences were observed by age in any wave across all organ and donor types. There was a higher proportion of female heart transplant recipients during the COVID-19 period. Conversely, there was a higher proportion of male lung transplant recipients and living donor liver recipients during the COVID-19 period. A lower proportion of heart transplant recipients, lung transplant recipients, and living donor liver recipients lived in neighborhoods in the lowest income quintile during the COVID-19 period when compared with the pre-COVID-19 baseline period. Finally, a lower proportion of living donor liver and kidney recipients lived in rural areas during the COVID-19 period when compared with the pre-COVID-19 baseline period (Table 2).

TABLE 2. - Baseline Characteristics of Solid Organ Transplant Recipients in the pre-COVID-19 Baseline Period Compared to the COVID-19 Period by Organ Type
Heart Lung Liver - living Liver- deceased donor Kidney- living donor Kidney- deceased donor
Pre-COVID COVID Pre-COVID COVID Pre-COVID COVID Pre- COVID COVID Pre-COVID COVID Pre-COVID COVID
N=200 N=77 SD N=508 N=150 SD N=122 N=77 SD N=601 N=235 SD N=690 N=235 SD N=1,468 N=513 SD
Age in years, median (SD) 54 (46-61) 54 (44-61) 0 62 (53-67) 62 (53-68) 0.08 55 (45-63) 57 (43-66) 0.02 59 (52-64) 59 (51-64) 0.03 49 (37-59) 51 (36-61) 0.09 58 (49-66) 56 (47-64) 0.15
Age 60 and over 59 (29.5) 26 (33.8) 0.09 298 (58.7) 85 (56.7) 0.04 48 (39.3) 32 (41.6) 0.05 286 (47.6) 110 (46.8) 0.02 162 (23.5) 66 (28.1) 0.11 682 (46.5) 205 (40) 0.13
Female 48 (24) 29 (37.7) 0.3 221 (43.5) 49 (32.7) 0.22 60 (49.2) 33 (42.9) 0.13 183 (30.4) 63 (26.8) 0.08 264 (38.3) 95 (40.4) 0.04 554 (37.7) 194 (37.8) 0
Male 152 (76) 48 (62.3) 0.3 287 (56.5) 101 (67.3) 0.22 62 (50.8) 44 (57.1) 0.13 418 (69.6) 172 (73.2) 0.08 426 (61.7) 140 (59.6) 0.04 914 (62.3) 319 (62.2) 0
Income quintile
 1 (lowest) 39 (19.5) 11 (14.3) 0.14 113 (22.2) 26 (17.3) 0.12 17 (13.9) ≤5 0.3 116 (19.3) 53 (22.6) 0.08 118 (17.1) 42 (17.9) 0.02 395 (26.9) 124 (24.2) 0.06
 2 29 (14.5) 12 (15.6) 0.03 100 (19.7) 34 (22.7) 0.07 18 (14.8) 8-10 (13) 0.05 130 (21.6) 48 (20.4) 0.03 117 (17) 48 (20.4) 0.09 315 (21.5) 122 (23.8) 0.06
 3 48 (24) 24 (31.2) 0.16 98 (19.3) 36 (24) 0.11 24 (19.7) 12 (16) 0.11 135 (22.5) 48 (20.4) 0.05 121 (17.5) 51 (21.7) 0.11 280 (19.1) 103 (20.1) 0.03
 4 40 (20) 14 (18.2) 0.05 97 (19.1) 29 (19.3) 0.01 24 (19.7) 17 (22.1) 0.06 114 (19.0) 50 (21.3) 0.06 148 (21.4) 45 (19.1) 0.06 269 (18.3) 98 (19.1) 0.02
 5 (highest) 44 (22) 16 (20.8) 0.03 97-99 (19) 25 (16.7) 0.07 39 (32.0) 34 (44.2) 0.25 102-104 (17) 33-35 (14) 0.07 181-183 (26) 49 (20.9) 0.13 205-207 (14) 63-65 (12) 0.04
 Missing ≤5 0 (0) ≤5 ≤5 0.02 ≤5 0 (0) 0.09 ≤5 ≤5
Rurality
 No 175 (87.5) 69 (89.6) 0.07 424 (83.5) 130 (86.7) 0.09 107 (87.7) 71 (92.2) 0.15 531 (88.4) 208 (88.5) 0 614 (89) 217 (92.3) 0.12 1,349 (91.9) 478 (93.2) 0.05
 Yes 25 (12.5) 8 (10.4) 0.07 80-84 (16) 20 (13.3) 0.08 15 (12.3) 6 (7.8) 0.15 67-69 (11) 24-26 (11) 0.01 72-74 (10) 18 (7.7) 0.11 119 (8.1) 35 (6.8) 0.05
 Missing ≤5 0 (0) 0.06 ≤5 ≤5 0.05 ≤5 0 (0) 0.08
All data presented as n (%) unless otherwise specified. Columns with values of 5 or less suppressed for privacy reasons. Standardized difference (SD) was used to compare baseline characteristics between study periods. Standardized differences of < 10% represent a negligible imbalance.

Short-Term Safety

Overall, 90-day mortality was 2.8% (n = 134; kidney 1.7% [n = 49]; liver 4.1% [n = 42]; lung 5.5% [n = 36]; heart 6.5% [n = 18]) during the study period. There was no difference in length of stay (11 days [interquartile range, 8–20 days] vs 11 days [interquartile range, 8–20 days]; P = 0.29), in-hospital mortality (2.3% n = 82 vs 2.5% n = 32; P = 0.65) or 90-day mortality (2.7% n = 97 vs 2.9% n = 37; P = 0.72) between those transplanted in the pre-COVID-19 period versus the COVID-19 period overall and for all solid organ types (Table 3). Emergency department visits and readmissions within 90 days after the index transplant admission were less frequent during all COVID-19 waves versus the pre-COVID-19 baseline period except for liver and heart recipients, where no differences were seen (Table 3). Similarly, there was no difference in transplant nephrectomy (5 or less [values of 6 or less suppressed for privacy reasons] vs 0.6% n = 12) or retransplantation rates (5 or less [values of 6 or less suppressed for privacy reasons] vs 0.9% n = 31) over 90 days across all COVID-19 waves and solid organ types, when compared with the pre-COVID-19 baseline period. Twenty-one (1.7%) solid organ transplant recipients were diagnosed with COVID-19 within 90 days of their transplant, 16 (76%) were hospitalized within 90 days.

TABLE 3. - Ninety-Day Outcomes Post-Transplantation
Index Admission Heart Lung Liver—Living Liver—Deceased Donor Kidney—Living Donor Kidney—Deceased Donor
Pre-COVID, N = 200 COVID, N = 77 P Pre-COVID, N = 508 COVID, N = 150 P Pre-COVID, N = 122 COVID, N = 77 P Pre-COVID, N = 601 COVID, N = 235 P Pre-COVID, N = 690 COVID, N = 235 P Pre-COVID, N = 1468 COVID, N = 513 P
In-hospital mortality 14 (7) ≤5 0.09 26 (5.1) 10 (6.7) 0.46 ≤5 ≤5 0.39 23 (3.8) 9 (3.8) 1 ≤5 0 (0) 0.56 15 (1.0) 7 (1.4) 0.52
Length of stay, median (IQR) 34 (17–63) 24 (15–47) 0.08 24 (17–41) 25 (17–49) 0.46 17 (12–27) 18 (11–31) 0.91 15 (10–33) 15 (10–30) 0.43 7 (7–9) 7 (7–9) 0.94 9 (7–13) 10 (8–13) 0.05
90-day outcomes
 Repeat ED visit 110 (55) 34 (44.2) 0.11 228 (44.9) 51 (34) 0.02 65 (53.3) 36 (46.8) 0.37 234 (38.9) 98 (41.7) 0.46 242 (35.1) 68 (28.9) 0.09 678 (46.2) 201 (39.2) 0.01
 Hospital readmission 104 (52) 33 (42.9) 0.17 201 (39.6) 46 (30.7) 0.05 51 (41.8) 33 (42.9) 0.88 177 (29.5) 77 (32.8) 0.35 182 (26.4) 53 (22.6) 0.25 549 (37.4) 165 (32.2) 0.03
 Retransplant ≤5 0 (0.0) 0.38 14 (2.8) ≤5 ≤5 ≤5 15 (2.5) ≤5 0 (0) 0 (0) 0 (0) ≤5
 COVID-19 diagnosis 0 (0) ≤5 0 (0) ≤5 0 (0) ≤5 0 (0) 6 (2.6) <0.01 0 (0) ≤5 0 (0) 6–10
 Death 12 (6) 6 (7.8) 0.59 22 (4.3) ≤5 ≤5 ≤5 26 (4.3) 11 (4.7) 0.82 ≤5 ≤5 0.62 30 (2) 13 (2.5) 0.51
All data are presented as n (%) unless otherwise specified. Values of 6 or less suppressed for privacy reasons. Outcomes were compared between periods using the χ2 and Kruskal-Wallis nonparametric tests where appropriate.
IQR indicates interquartile range.

DISCUSSION

The COVID-19 pandemic and resultant policy response had a substantial impact on the rates of solid organ transplantation in Ontario with a 24.3% decrease or 409 fewer transplants compared with a 3-year pre-COVID-19 baseline period. However, not all transplantation services were impacted equally, with no sustained changes observed in the rates of heart or liver transplantation, while sustained and large decreases were seen for lung and kidney transplantation. Several factors likely contributed to this decrease in transplantation activity, including concerns about the potential risk of transmitting COVID-19 to heavily immunosuppressed transplant recipients and otherwise healthy living donors, both of which were major drivers of early restrictions on transplant activity. Interestingly, there were no differences in 90-day outcomes after transplantation during the COVID-19 period, including no change in hospital length of stay, complications, in-hospital and 90-day mortality, and retransplantation. This finding must be highlighted as transplantation was provided safely even during the midst of a pandemic. We observed a lower proportion of transplant patients presenting to the ED during the COVID-19 period, likely a reflection of avoidance of hospitals and EDs when levels of COVID-19 infection were high. In those that did present, we did not observe an increase in the proportion of readmissions.

The impact on transplant activity of the COVID-19 pandemic in Ontario was similar to that observed in other jurisdictions. Worldwide transplant activity decreased during the pandemic, with kidney transplantation being the most affected, followed by lung, liver, and heart.1 This finding is partially concordant with what was observed in Ontario. The overall transplant rate and the specific rates for kidney and lung transplantation decreased during the COVID-19 pandemic. However, no significant differences were observed in the rates of liver and heart transplantation in contrast to the 10.6% and 5.4% decreases observed worldwide for these organs, respectively.1 In the United States, liver transplantation decreased from 68% in March to 52% in May 2020 and from 73% to 42% for living and deceased donors, respectively.10 Similarly, the United States heart transplant volume decreased by 26% nationally from the pre–COVID-19 era to the COVID-19 era.11 This was accompanied by increased waitlist inactivations, decreased waitlist additions, and decreased donor recovery.11 In contrast, in the United Kingdom, although abdominal organ transplants (particularly kidneys) were substantially reduced during the COVID-19 pandemic compared with the same period in 2019, heart transplant activity was relatively unaffected.12 Similarly, in Australia, despite experiencing a significantly lower incidence of COVID-19 during 2020, kidney transplantation activity decreased by 27% compared with 2019, with lesser reductions in liver (8%) and lung (12%). Interestingly, heart transplant activity increased by 26% during the same period.

Differences in the transplant recipients’ characteristics were observed between the historical and COVID-19 period in Ontario. Differences in the age in kidney transplant recipients are explained by the restrictions placed on transplant activity, such as the initial restrictions regarding the use of extended criteria donors, while uncertainty around COVID-19 remained high. The higher proportion of female heart transplant recipients observed during the COVID-19 period may reflect changes in the deceased donor population, with fewer trauma death donors during the COVID-19 pandemic. These latter donors are predominantly male, as observed in the United States.13 However, differences observed in the sex of living donor liver and lung transplant recipients, and the lower proportion of some transplant recipients (ie, heart, lung, and living donor liver and kidney) from low-income neighborhoods as well as rural areas, may reflect barriers to accessing transplantation during the COVID-19 period. It is possible that COVID-19 worsened pre-existing barriers to transplantation.14 Lower income has been previously associated with being less likely to undergo living donor liver transplantation in Ontario.15 Lower income and receiving dialysis at a location >100 km from a transplant center have also been associated with a lower likelihood of referral for kidney transplantation.16

Our results demonstrated a relatively low COVID-19 infection prevalence (1.7%) within 90 days of transplantation and no differences in post-transplant hospital length of stay, mortality (in-hospital and 90-day), and retransplantation/transplant nephrectomy between the COVID-19 period and the historical comparison period. Up to October 3, 2021 (end of study period) only 3.9% of the Ontario population had been diagnosed with COVID-19, our findings of a 1.7% prevalence of COVID-19 diagnosis in the 90 days after transplant can be due to increased testing in asymptomatic patients, increased susceptibility due to immunosuppression, or increased healthcare interactions during the peritransplant period. Previous reports demonstrated a higher incidence and mortality of COVID-19 infections during the early post-transplant period, albeit these were early experiences during the pandemic in countries with a very high prevalence of COVID-19 infections prior to availability of vaccines. A prospective cohort study of Spanish kidney transplant recipient between March 2020 and April 2020 indicated a cumulative incidence of COVID-19 infection of 9% within 60 days of transplantation and a fatality rate of 45.8%.17 Similarly, an early report of patients who underwent liver transplantation between February 2020 and April 2020 in the Lombardy region of Italy demonstrated a COVID-19 infection incidence of 11.7% and a 5.9% fatality rate at 30 days.18 The lower proportion of transplant patients presenting to the ED and being readmitted during the COVID-19 period is in keeping with several other studies examining emergency general surgery presentations during the COVID-19 pandemic, including previous reports by our group.19,20 This phenomenon likely reflects the avoidance of hospitals and the EDs by patients when levels of COVID-19 infections were high.

A major strength of this study is the population-based nature of the data sources, which allowed for large sample sizes and the ascertainment of complete outcomes. There are limitations in this study that are inherent to the datasets available at ICES. We were unable to capture changes in rates of deceased and/or living organ donation due to limitations in the data. We did not ascertain whether the rate of virtual or in-person outpatient clinic appointments changed during the study period affecting visits to the ED. We also acknowledge the possibility of incomplete ascertainment of COVID-19 infections. Nonetheless, we used the best available data for this purpose.

The COVID-19 pandemic had unprecedented impact on solid organ transplantation, and Ontario was no exception. While early safety concerns warranted a precautionary approach limiting transplantation to immediate life-saving procedures, the reduction in the rate of some transplants continued for the rest of the pandemic, where no restrictions were in place. This finding raises the question of whether additional emphasis must be placed on prioritizing solid organ transplantation during subsequent COVID-19 waves as well as during the next pandemic. While transplant volumes were not affected for liver and heart transplantation, including living donor liver transplantation, kidney transplantation was particularly affected potentially due to its nonimmediate life-saving nature and the possibility to postpone transplantation with dialysis. However, the number of life-years saved per kidney transplant is akin to the number of life-years saved per liver transplant.21,22 The differential effect of the COVID-19 pandemic on the kidney transplant volumes initially reflected safety concerns but then constraints on health system resources likely became a major driving force. The significant and continuing decline in the rate of kidney transplant should prompt review of intake, assessment, and allocation mechanisms to correct this and prevent the same from occurring during the next pandemic.

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Keywords:

COVID-19; heart transplant; kidney transplant; liver transplant; lung transplant; solid organ transplantation

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