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Original Clinical Science—General

Trends in Lung Transplantation Practices Across the United States During the COVID-19 Pandemic

Chan, Ernest G. MD, MPH1; Chan, Patrick G. MD, MPH1; Harano, Takashi MD1; Ryan, John P. PhD1; Morrell, Matthew R. MD2; Sanchez, Pablo G. MD, PhD1

Author Information
doi: 10.1097/TP.0000000000003522

Abstract

INTRODUCTION

Solid organ transplant centers across the United States have been faced with the challenges of balancing patient and healthcare worker safety along with hospital resources since the start of the coronavirus disease 2019 (COVID-19) pandemic.1-5 Many transplant centers have restricted their services by deactivating waitlist patients as a response to the mortality and morbidity associated with the pandemic and only providing transplants to their sickest patients. As centers begin to return to normal clinical practice, there is need to reflect on the substantial reduction in transplant volume during the COVID-19 pandemic to better prepare for the future.6

Utilizing data provided by the United Network for Organ Sharing (UNOS) organization, DeFlippis et al7 reported heart transplantation trends in the United States during the current pandemic. When comparing to a predetermined pre-COVID-19 versus the COVID-19 era, they saw a significant reduction in volume, waitlist additions, and donor recovery in the context of heart transplantation in the United States. Currently, there is limited literature regarding national and regional trends in lung transplantation (LT) practices. Therefore, the purpose of this study is to examine the effects of the COVID-19 pandemic on adult LT waitlists and volumes in the United States.

MATERIALS AND METHODS

We performed a cross-sectional study analyzing data provided by UNOS to identify trends in adult (≥18 y) LT services across the United States from January 1, 2020 to June 30, 2020.8 This publicly available dataset was provided on the UNOS website to offer insight into practice changes in solid organ transplantation in the United States and is separate from the UNOS Standard Transplant and Analysis Registry (STAR) file and does not have any of the STAR file data.8 This data was presented on several levels including the national level as well as the 8 prespecified UNOS regions introduced in the context of COVID-19.7,8 Pediatric LT data were excluded. Weekly reported data were collected included the following: waitlist inactivations (COVID-19 precautions or not), waitlist additions, transplantation volume, and adult deceased donor recovery data for all organs. Institutional review board (IRB) approval and informed consent were not required for the completion of this study due to the deidentified nature of the data.

Case rates per 100 000 persons by state from January 22, 2020 to June 30, 2020 were obtained from the US Center for Disease Control and Prevention (CDC).9 Time periods were defined in accordance to practices established by UNOS. March 15, 2020 was utilized to differentiate the end of the pre-COVID era as this was the date at which the UNOS began identifying waitlist activations due to COVID-19 precautions. For equal comparison purposes, each time period was split into 8-wk periods corresponding to 3 time periods: pre-COVID-19 (January 19, 2020–March 14, 2020), first COVID-19 (March 15, 2020–May 8, 2020), and second COVID-19 eras (May 9, 2020–June 30, 2020). Although the COVID-19 pandemic was ongoing throughout all 3 eras, the differentiation of eras allowed us to characterize the national response to the pandemic as the flow of information increased.

Statistical Analysis

A repeated measure generalized linear mixed model was used to analyze differences in organ utilization between eras. Weekly reporting of inactivations, new waitlist additions, adult deceased donor recovery, and LT volume were used as the outcome. The model utilized a negative binomial distribution, with an AR1 covariance structure to account for the temporal nature of the data. Region and era were entered as fixed effects along with an interaction term between the region and era. Region was additionally entered as a random effect with a random intercept. Post hoc comparisons were performed using pairwise comparisons, and multiple comparison correction was performed by least significant difference. Post hoc P values were multiple comparison adjusted. To examine relationships between changes in COVID-19 precaution inactivations, waitlist additions, and transplant volumes, difference scores were calculated for the total number of cases in each variable. Bivariate correlations were then performed between the difference scores. An adjusted P value <0.05 was considered statistically significant. Data were analyzed using SPSS GENLINMIXED (Build 1.0.0.1327; IBM, Armonk, NY).

RESULTS

Nationally, confirmed cases of COVID-19 increased dramatically from 0.88 to 776.05 cases per 100 000 persons from March 15, 2020 to June 30, 2020. There was a gradual decrease in COVID-19 positive cases from the first and second COVID-19 eras from weeks 14 to 21, with an additional spike starting week 22 (Figure S1, SDC, http://links.lww.com/TP/C50). The highest case rate shifted from the Northwest and Northeast regions (2.76 and 1.83 cases per 100 000 population, respectively) to the Northeast and Mid-Atlantic (1731.17 and 767.19 cases per 100 000 population, respectively) by June 30, 2020 (Table 1). There were no associations between changes in the weekly reported incidences of COVID-19+ cases between each era and waitlist inactivations due to COVID-19 precautions, new waitlist additions, LT volume, or deceased donor recovery (Table S1, SDC, http://links.lww.com/TP/C50).

TABLE 1. - National and regional trends in COVID-19 cases, and lung transplant waiting list inactivations and additions, adult deceased donor recovery, and volume
Pre-COVID-19 era vs first COVID-19 era
Region All waitlist inactivations New waitlist additions Adult deceased donor recovery Transplant volume
1/22–3/14COVID-19 case rate per 100 000 people Pre-COVID-19 First COVID-19 Waitlist inactivation due to COVID-19, No. (%) Pre-COVID-19 First COVID-19 Pre-COVID-19 First COVID-19 Pre-COVID-19 First COVID-19
Northwest 2.76 7 6 −14.29 3 (50) 4 4 0.00 77 59 −23.38 11 6 −45.45
North Midwest 0.65 17 53 211.76 38 (71.7) 38 13 −65.79 181 105 −41.99 29 18 −37.93
Great Lakes 0.36 80 135 68.75 106 (78.52) 105 48 −54.29 285 205 −28.07 85 44 −48.24
Northeast 1.83 16 113 606.25 106 (93.81) 60 23 −61.67 184 110 −40.22 38 6 −84.21
Mid-Atlantic 0.40 46 54 17.39 39 (72.22) 66 52 −21.21 214 176 −17.76 64 35 −45.31
Southwest 1.03 51 56 9.80 34 (60.71) 70 54 −22.86 313 251 −19.81 103 66 −35.92
South Midwest 0.17 25 35 40.00 19 (54.29) 43 37 −13.95 182 152 −16.48 34 31 −8.82
Southeast 0.51 23 44 91.30 30 (68.18) 99 69 −30.30 441 319 −27.66 90 71 −21.11
United States 0.88 258 496 92.25 375 (75.6) 485 301 −37.94 1867 1382 −25.98 458 277 −39.52
Pre-COVID-19 era vs second COVID-19 era
Region 1/22–6/30 COVID-19 case rate per 100 000 people Second COVID-19 a Waitlist inactivation due to COVID-19, No. (%) Second COVID-19 a Second COVID-19 a Second COVID-19 a
Northwest 201.48 7 0.00 0 (0) 7 75.00 68 −11.69 6 −45.45
North Midwest 594.12 8 −52.94 0 (0) 27 −28.95 157 −13.26 23 −20.69
Great Lakes 724.8 46 −42.50 1 (2.17) 63 −40.00 264 −7.37 74 −12.94
Northeast 1731.17 22 37.50 7 (31.82) 43 −28.33 157 −14.67 41 7.89
Mid-Atlantic 767.19 27 −41.30 1 (3.7) 49 −25.76 205 −4.21 54 −15.63
Southwest 657.45 23 −54.90 2 (8.7) 63 −10.00 307 −1.92 75 −27.18
South Midwest 527.08 13 −48.00 1 (7.7) 38 −11.63 187 2.75 47 38.24
Southeast 717.15 15 −34.78 0 (0) 73 −26.26 466 5.67 80 −11.11
United States 776.05 162 −37.21 12 (7.41) 359 −25.98 1794 −3.91 400 −12.66
a% Δ was calculated for the postinitial COVID-19 era in reference to the pre-COVID-19 era.

National and Regional Trends in LT Practices

Waitlist Inactivations

There was a significant change in inactivations across the 3 eras [F (2, 168) = 13.76, P < 0.001]. Two hundred fifty-eight waitlist inactivations occurred during the pre-COVID-19 era while 496 occurred in the first COVID-19 era, a 92.25% increase (t = 2.82, P = 0.005) (Table 1) (Figure 1A). The Northeast (113, 606.25%) followed by the North Midwest (53, 211.76%) had the highest increase in inactivations. The Southwest and North Midwest regions experienced the highest decreases in waitlist inactivations (−54.90% and −52.94%, respectively) (Table 1). Overall waitlist inactivations significantly decreased entering the second COVID-19 era (t = 3.60, P < 0.001). In comparison with the pre-COVID-19 era, there was a decrease in waitlist inactivations nationally in the second COVID-19 era, but the difference was not statistically significant (258 versus 162, −37.21%, P = 0.10). There was no main effect of region [F (7, 168) = 1.77, P = 0.10], and the interaction between region and era was nonsignificant [F (14, 168) = 1.01, P = 0.44] indicating that there were not significant differences across regions in rates of change.

FIGURE 1.
FIGURE 1.:
The COVID-19 pandemic has affected various key elements regarding lung transplantation in the United States. Presented above are national trends in lung transplant waitlist inactivations (A), new waitlist additions (B), adult deceased donor recovered (C), and lung transplant volume (D).

For COVID-19 precautions inactivations, the dataset was limited to the first and second COVID-19 eras. Three hundred seventy-five (75.6%) of all inactivations during the first COVID-19 era were categorized as due to COVID-19 precautions. There was a trend toward more COVID-19 related inactivations during the first COVID-19 era [F (1, 112) = 3.79, P = 0.054]. There was no main effect of region [F (7, 112) = 0.92, P = 0.50] and no interaction between era and region [F (7, 112) = 0.37, P = 0.92] indicating that there were not significant differences between regions, nor were there differences between regions in rates of change.

New Waitlist Additions

There was a significant change in new waitlist patients across all 3 eras [F (2, 168) = 5.64, P = 0.004] with a significant decrease in listings transitioning to the first COVID-19 era (t = 3.30, P < 0.001). During the first COVID-19 era, 301 patients were added to the LT waitlist, representing a decrease of nearly 40% in the United States from the prior 8-wk period. All UNOS regions except the Northwest (Δ 0%) experienced a decrease in waitlist additions (range 0%–65.79%). The North Midwest (37 pre-COVID-19 versus 13 COVID-19 era, −65.79%) and the Northeast (105 pre-COVID-19 versus 48 COVID-19 era, −61.67%) experienced the highest decrease in waitlist additions. Following week 17, a significant increase in listings occurred into the second COVID-19 era (t = 2.16, P = 0.032) (Figure 1B). There was a significant main effect of region [F (7, 168) = 16.83, P < 0.001]. Waitlist additions trends across the nation were similar across all regions [F (14, 168) = 0.92, P = 0.54], and there was no difference between the pre-COVID-19 and second COVID-19 eras (t = 0.97, P = 0.16). From the pre-COVID to the first COVID era, higher amounts of COVID inactivations were associated with a greater decrease in new waitlist listings [r (8) = −0.88, P = 0.002], while a larger decrease in COVID inactivations was associated with a larger increase in waitlist listings [r (8) = −0.76, P = 0.030] when the nation transitioned from the first to second COVID-19 era.

Adult Deceased Donor Recovery

There was a significant change in deceased adult donors recovered across the 3 study eras [F (2, 168) = 27.00, P < 0.001]. Deceased adult donor recovery significantly decreased from the pre-COVID-19 to first COVID-19 era (range −16.48% to −41.99%, t = 6.46, P < 0.001) (Table 1). The North Midwest (−41.99%) and the Northeast (−40.22%) experienced the highest decreases in the utilization of adult deceased donors during the first COVID-19 era. After week 12, the utilization of adult deceased donors began to increase and significantly increased afterward into the second COVID-19 era (t = 7.85, P < 0.001) (Figure 1C). There was not a significant difference between pre-COVID-19 and second COVID-19 eras (t = 1.39, P = 0.17). There was a significant main effect of region [F (7,168) = 7.81, P < 0.001]. The interaction between region and era was nonsignificant [F (14, 168) = 0.85, P = 0.61].

LT Volume

There was a significant change in adult cases across the 3 eras [F (2, 168) = 10.91, P < 0.001] with a significant drop in cases from the pre-COVID-19 era (t = 4.83, P < 0.001). During the first COVID-19 era, 277 LTs were performed, representing a nearly 40% decrease compared to the pre-COVID-19 era (Figure 1D). The Northeast experienced the largest percentage decrease in cases performed at 84.21% (38 pre-COVID-19 versus 6 first COVID-19 era) followed by the Great Lakes (85 pre-COVID-19 versus 44 first COVID-19 era, −48.24%). The South Midwest region experienced the lowest decrease in LT volume in the first COVID-19 era (34 versus 31, −8.82%) (Table 1).

While the national LT volume increased following the first COVID-19 era (t = 3.33, P = 0.001) was not statistically different from baseline (t = 1.30, P = 0.20), the 400 LTs performed in the most recent era represents a 12.66% decrease in overall LT volume in comparison to the pre-COVID-19 era. The South Midwest region experienced the highest increase in LT volume compared to the pre-COVID-19 era (+38.24%). Other notable regions include the Northwest and Southwest regions where there was a 45.45% and 27.18% decrease in volume, respectively (Table 1). While there was also a significant effect of region [F (7, 168) = 23.50, P < 0.001], there was no interaction between region and study era [F (14, 168) = 1.22, P = 0.27] regarding LT volume.

There was no association between changes in LT volume and new waitlist additions (P = 0.06 and 0.22, respectively) as well as deceased donor recovery (P = 0.35 and 0.97, respectively) transitioning from the pre-COVID-19 to the first COVID-19 era and from the first to second COVID-19 era. However, weekly changes in volume was negatively associated with to the use of waitlist inactivations due to COVID-19 precautions during both transitions (r = −0.73, P = 0.04; r = −0.89, P = 0.003) (Figure 2).

FIGURE 2.
FIGURE 2.:
The effects of the COVID-19 pandemic on national lung transplant volumes varied based on the UNOS designated regions. Presented above are associations between changes in lung transplant volume and COVID-19 inactivations transitioning from the pre-COVID-19 to first COVID-19 eras (A) and from the first COVID-19 to second COVID-19 eras (B).

DISCUSSION

Due to the current COVID-19 pandemic, the United States will likely experience one of the first substantial decreases in annual volume in many years.10 Interestingly, no variables analyzed in this study were associated with the trends in COVID-19 cases across all regions. With this dataset, it is rather difficult to identify the exact rationale for the changes in LT practices during the pandemic. Current trends suggest the decrease in LT volume was not associated with any trends in COVID-19 positive cases across the United States. We found that the decrease in LT volume was associated with a number of practice changes, one of which was the use of waitlist inactivations due to COVID-19 precautions. Interestingly, the use of this option was not associated with any trends in COVID-19 positive cases in any region. While our analysis is not equipped to further analyze this relationship, we suspect that a better understanding of the COVID-19 virus and improved management and identification of COVID-19 patients may have encouraged the disuse of this inactivation option. Therefore, moving forward while COVID-19 cases continue to rise, the use of evidence-based medicine to identify when the use of inactivating patients due to COVID-19 precautions is necessary to allow the US LT programs to continue offering their services

While transplant centers have greatly moved away from inactivating patients due to COVID-19 precautions, waitlist characteristics as well as the use of adult deceased donors may affect LT volume moving forward. Waitlist additions, for example, are dependent on referrals from pulmonary specialists and primary care physicians who initially evaluate patients for transplant eligibility. Because outpatient visits have decreased significantly, a decrease in referrals will likely continue and may have lingering effects on all waitlists across the country.11,12 While there was no association between weekly LT volume and new waitlist additions, there may be downstream effects not identified in our statistical analysis. Based on our experience, because of the low incidence of COVID-19 in western Pennsylvania, the LT program at the University of Pittsburgh Medical Center remained active during COVID-19 era with an increase in donor offers in all 3 study periods by as much as 55% when compared to 2019 with no decrease in volume. However, because evaluation referrals decreased significantly from an average of 60 to 20 patients over the past 5 mo, our waitlist census is the lowest within the last 2 decades.

Anecdotally, LT centers closed in the earlier states deemed “hotspots” by the CDC restricted transplant services very early on. States such as New York likely acted quickly as their resources were all overwhelmed by patients who contracted the COVID-19 virus. However, statistically, we found there were no associations between region and study era. These results support the notion that several factors including the local epidemiology of COVID-19, geographic concerns, are taken into consideration when halting LT services. Therefore, further studies will likely be necessary to identify these associations.

With a potential second wave of COVID-19 in the United States, an important area that may need to be addressed is improving the communication lines among surgeons, pulmonologists, and primary care physicians to refer patients with end-stage pulmonary disease to the proper LT specialists. This will require patients to obtain preoperative testing and social distancing. However, the use of telemedicine can hopefully minimize their chances of exposure to the virus. Several other disciplines have published their practice pattern changes with the incorporation of telemedicine and other technology-based ways of communication in the era of COVID-19 while not compromising care.13-15

Currently, UNOS echoes the American Society of Transplantation’s recommendations published on May 14, 2020 to continue COVID-19 testing despite acknowledging that no current test is 100% sensitive or specific and that false positives and negative results may occur.16 The American Society of Transplantation guidelines stratify donors into donors without risk factors, those with intermediate risk factors, and deceased donors with active infection, high risk, or who test SARS-CoV-2 positive. The ambiguous area which requires good clinical judgment is organs from deceased donors with intermediate risk factors. These donors reside in areas with some epidemiologic risk factors or may have exhibited some clinical symptoms suggestive of COVID-19 infection. Testing is mandatory in these patients with intermediate risk factors especially those with clinical symptomatology or potential iatrogenic or community exposure. In addition to testing, these intermediate risk donors should require additional investigation into either CDC reported incidence of COVID-19 cases in the area surrounding the donor hospital or inquiry with the medical staff at the donor hospital. Donors that may have been suitable for lung transplantation should be turned down either due to elements in their history or location in a CDC determined hotspot which would increase their risk of being a COVID-19 positive patient. While the use of adult deceased donors has continued to trend back to similar levels as the pre-COVID-19 era, only time will tell whether this caution will continue to restrict transplant centers from accepting offers especially in the setting of a second rise of COVID-19 cases nationally.

Limitations

Due to the retrospective nature of this study, there are limitations including reporter bias. In addition, because there is no current ability to link the data being analyzed to the full UNOS dataset regarding LT in the United States, our analysis is limited to just the specified variables provided. However, we hope that this article invites the conversation to further devoting resources to how the COVID-19 pandemic has affected lung transplantation in the United States and allow for more detailed datasets to be analyzed.

In conclusion, the importance of identifying LT volume and waitlist trends during the COVID-19 era lies in identifying areas that will need to be bolstered in the upcoming months. While we hope to see a downward trend of COVID-19 cases worldwide, implementing policy and practice changes to all aspects of lung transplantation will ultimately be needed to continue to grow lung transplantation across all regions of the United States.

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