COVID-19's impact on heart and lung transplantation: Citation-based analysis of research output

Abstract

BACKGROUND

Since being declared as a pandemic on March 11, 2020, coronavirus disease 2019 (COVID-19) has profoundly influenced heart and lung transplant programs, impacting donor availability, patient management, and healthcare resources. This study offers a citation-based review of the research output on this subject, seeking to understand how the transplant community has responded to these challenges. Through a review of literature from the beginning of the pandemic to early 2023, we evaluate the shifts in academic emphasis and the emerging trends in heart and lung transplantation during the COVID-19 period.

AIM

To assess the impact of COVID-19 on heart and lung transplantation research, highlighting key themes, contributions, and trends in the literature during the pandemic.

METHODS

We conducted an extensive search of the Web of Science database on February 9, 2023. We employed the terms "transplant" and "transplantation", as well as organ-specific terms like "heart", "cardiac", and "lung", combined with COVID-19-related terms such as "COVID-19", "coronavirus", and "SARS-CoV-2". The search encompassed publications from March 11, 2020 to February 9, 2023. Data on authors, journals, countries, institutions, and publication types (articles, reviews, conference papers, letters, notes, editorials, brief surveys, book chapters, and errata) were analyzed. The data was visualized and processed with VOSviewer 1.6.18 and Excel.

RESULTS

We included 847 research items. There were 392 articles (46.3%) and 88 reviews (10.3%). The studies included were referenced 7757 times, with an average of 9.17 citations per article. The majority of the publications (n = 317) were conducted by institutes from the United States with highest citations (n = 4948) on this subject, followed by Germany, Italy, and France. The majority of papers (n = 101) were published in the Journal of Heart and Lung Transplantation.

CONCLUSION

To the fullest extent of our knowledge, this is the first bibliometric study of COVID-19's impact on heart and lung transplantation to offer a visual analysis of the literature in order to predict future frontiers and provide an overview of current research hotspots.

Key Words: COVID-19; Pandemic; Heart transplant; Lung transplant; Bibliometric analysis

Core Tip: The coronavirus disease 2019 (COVID-19) pandemic, which started on March 11, 2020, has had a huge impact on heart and lung transplant programs. We performed an extensive search in the Web of Science database, utilizing keywords associated with transplantation and COVID-19, encompassing publications from March 11, 2020, to February 9, 2023. We analyzed data on authors, journals, countries, institutions, and different types of publications using VOSviewer 1.6.18 and Excel for visualization and data manipulation. The study encompassed a total of 847 research items, consisting of a substantial number of articles and reviews. The average citation rate per article was 9.17. The majority of publications were from United States institutions, which also had the highest citation count, followed by Germany, Italy, and France. This bibliometric study is the first to give a full picture of how COVID-19 has affected heart and lung transplants, showing where more research is needed and where it should go in the future.

INTRODUCTION

The emergence of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, sparked a global health crisis that significantly affected healthcare systems worldwide, particularly in the domain of solid organ transplantation[1,2]. Orthotopic heart transplant (OHT) and orthotopic lung transplant (OLT) are recognized as critical interventions for patients with end stage cardiac and lung diseases. Nevertheless, the emergence of COVID-19, a multisystem illness predominantly resulting in mortality due to respiratory failure and considerable cardiovascular complications, presented unparalleled challenges to these life-saving procedures[3-5].

At the peak of the pandemic, the field of heart and lung transplantation experienced considerable disruptions[6,7]. The logistics of organ donation were modified, resulting in limited organ availability and changes in transplantation practices[8]. For example, there was a noticeable shift in patient demographics, as more individuals with severe COVID-19-related acute respiratory distress syndrome became candidates for OLT[7]. Moreover, the consequences extended logistical challenges, involving alterations in patient management approaches and post-transplant care related to the concerns linked to immunosuppression and viral transmission[7].

This study aims to provide a comprehensive bibliometric analysis of the global research output regarding the impact of COVID-19 on OHT and OLT. By examining the literature during the pandemic, this analysis identifies key themes, influential studies, and shifts in research focus over time. The goal is to highlight how the pandemic has shaped current research priorities and to identify areas where further study is needed to enhance the resilience of heart and lung transplantation practices against future global health crises.

MATERIALS AND METHODS

Data collection and retrieval methods

On February 15, 2023, we searched the web of science database using the terms “transplant” and “transplantation” and organ-related terms like “heart”, “cardiac”, “lung”, in addition to COVID-19 terms such as “COVID-19”, “coronavirus”, and “SARS-CoV-2”. The exact algorithm was: (TOPIC "lung transplant" OR "heart transplant" OR "cardiac transplant" AND TOPIC ("COVID-19" OR "COVID" OR "CORONAVIRUS" OR "SARS-COV-2")).

Articles, reviews, conference papers, letters, notes, editorials, brief surveys, book chapters, and errata were included. Articles with missing information were manually removed from the spreadsheet. All the included articles were in the English language. The search query ranged from March 11, 2020 to February 9, 2023.

Statistical analysis

The quantity of citations constituted the foundation for all analyses. We utilized VOSviewer version 1.6.18 and Microsoft Excel to analyze annual trends, countries, institutions, authors, journals, keywords, and articles, generating tables and figures. The studies included and excluded were illustrated through a flowchart.

VOSviewer network visualization interpretation

The components in the network visualization are represented as circles. The dimension of the circle of the term is dictated by its weight. The circumference of the circle expands in proportion to its mass. The cluster to which an item is assigned dictates the object's color. Lines between items indicate connections. The spatial separation between two circles in the visualization approximately indicates the degree of relatedness of the terms they represent, based on co-citation relationships. The closer two circles are, the more likely they are to be interconnected. The lines illustrate the most robust co-citation relationships among the circles.

RESULTS

Included studies

Of the 847 search results, we included them all. In terms of the research document type, 392 studies were articles, 88 of the studies were reviews, while the remaining studies were conference papers, editorials, errata, letters, notes, and proceeding papers (n = 367). In total, the included studies were cited 7757 times, and 5923 without self-citations with a mean (SD) of 9.17 citations per article.

Annual trends

The studies were published between 2020 and 2023, encompassing the onset of the pandemic through the conclusion of our search period. In the years 2020, 2021, 2022, and 2023, the number of studies was 139 (16.41%), 315 (37.19%), 379 (44.74%), and 12 (1.41%), respectively.

Countries

The majority of the documents were conducted by institutions from the United States (n = 317), which had the highest citations number (n = 4948) on this topic, followed by Germany, Italy and France. Table 1 shows publications and citations of the top-contributing countries. Figure 1 illustrates the contribution of each country and their interconnections. There were seven main clusters, with the largest comprising Belgium, Denmark, England, Greece, Israel, Poland, Portugal, Russia, Spain and Sweden.

Figure 1 The visualization of each country’s contribution and their interconnections.

Table 1 Publications and citations of the top-contributing countries.

Country	Documents	Citations
United States	379	4948
Germany	58	574
Italy	58	461
France	46	387
Canada	43	294
China	39	560
India	35	136
Spain	33	401
Brazil	29	99
England	23	137
Austria	22	272
Poland	22	38
Netherlands	20	111
Belgium	18	142

Institutions

The three institutions with the highest total number of publications were Northwestern University (n = 26) and Columbia University (n = 21) from the United States, University of Toronto (n = 19) from Canada. With respect to the number of citations, Columbia University had the highest number of citations (n = 2669), Harvard medical school (n = 1586), Icahn medical school (n = 1454). Supplementary Table 1 shows publications and citations of the top-contributing institutions. Figure 2 shows the top-cited institutions and their interconnections between the clusters.

Figure 2 Network visualization showing the top-cited institutions and their interconnections between the clusters.

Authors

Our analysis encompassed a total of 5262 authors. Among them, six authors contributed to at least ten documents concerning transplantation and COVID-19, while seventy-one authors were involved in at least five documents. The top five authors in terms of citation were Bharat A with 295, Budinger G, Manerikar A, and Kurihara C with 269 citations each, and Hoetzenecker K with 180 citations on their COVID-19 transplantation publications with a total of 1282 times. The comprehensive list of the most-cited authors is displayed in Supplementary Table 2.

Journals

Most publications were published in the Journal of Heart and Lung Transplantation (n = 101), American Journal of Transplantation (n = 50), and Clinical Transplantation (n = 29). Circulation published 9 articles on the topic however it received the highest number of citations (n = 979), followed by American Journal of Transplantation (n = 956) and Journal of Heart and Lung Transplantation (n = 811) for papers addressing transplantation in the context of COVID-19. Table 2 shows the most publishing journals in the field of heart transplant and lung transplant in the context of COVID-19.

Table 2 The most publishing journals.

Journal	Documents	Citations
Journal of Heart and Lung Transplantation	168	811
American Journal of Transplantation	50	956
Clinical Transplantation	29	186
Transplantation Proceedings	29	49
Transplant Infectious Disease	25	172
Transplantation	25	254
Transplant International	16	18
American Journal of Respiratory and Critical Care Medicine	11	1
European Journal of Heart Failure	11	72
Chest	10	20
Circulation	9	979
Annals of Thoracic Surgery	8	34
Esc Heart Failure	8	24
Journal of Thoracic and Cardiovascular Surgery	8	56
Lancet Respiratory Medicine	8	280

Top-cited articles

The top 10 most-cited articles are listed in Table 3[9-18]. “Post-acute COVID-19 syndrome” published by Nalbandian et al[9] in Nature Medicine, was the most cited study (n = 1357), followed by “COVID-19 and Cardiovascular disease” by Clerkin et al[10], which was published in Circulation (n = 946). The third most-cited article (n = 135) was “Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID-19 pneumonia in Wuhan, China” by Li et al[11], which was published in Histopathology.

Table 3 List of the top-ten most cited articles.

Ref.	Year	Title	Journal	Cited by
Nalbandian et al[9]	2021	Post-acute COVID-19 syndrome	Nature Medicine	1357
Clerkin et al[10]	2020	Covid-19 and Cardiovascular disease	Circulation	946
Li et al[11]	2020	Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID-19 pneumonia in Wuhan, China	Histopathology	135
Bharat et al[12]	2020	Successful recovery of COVID-19 pneumonia in a Lung transplantation for patients with severe COVID-19	Science Translational Medicine	133
Latif et al[13]	2020	Characteristics and Outcomes of Recipients of Heart Transplant With Coronavirus Disease 2019	JAMA Cardiology	121
Raja et al[14]	2021	COVID-19 in solid organ transplant recipients: A systematic review and meta-analysis of current literature	Transplantation Reviews	117
Chen et al[15]	2020	Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis	Chinese Medical Journal	104
Coll et al[16]	2021	COVID-19 in transplant recipients: The Spanish experience?	American Journal of Transplantation	104
Bharat et al[17]	2021	Early outcomes after lung transplantation for severe COVID-19: A series of the first consecutive cases from four countries	The Lancet	97
Marinaki et al[18]	2021	Immunogenicity of SARS-CoV-2 BNT162b2 vaccine in solid organ transplant recipients	American Journal of Transplantation	83

Keywords

The 10 most frequently used keywords related to transplantation and COVID-19 are analyzed, with ten appearing more than 200 times each: (1) “Outcomes”; (2) “Immunosuppression”; (3) “Respiratory-distress syndrome”; (4) “Extracorporeal membrane oxygenation”; (5) “Impact”; (6) “Vaccination”; (7) “Survival”; (8) “Acute respiratory distress syndrome”; (9) “Pulmonary fibrosis”; and (10) “Pandemics”. Figure 3A shows the most frequently used keywords across the years as a cluster visualization. Interestingly, the term vaccination and vaccine were most frequently discussed more recently toward the end of 2021 as shown in the overlay Figure 3B.

Figure 3 Network visualizations of keyword frequency. A: It presents a network visualization depicting the most frequently occurring keywords within the dataset, illustrating the interconnections and prominence of each term; B: It offers an overlay network visualization that highlights the most occurring keywords, with an emphasis on their distribution and changes over time, providing insights into temporal trends and shifts in keyword significance.

DISCUSSION

The COVID-19 pandemic affected organ donation and transplant programs around the world. This paper’s main goal is to provide a bibliometric analysis and annual trends of OHT and OLT and COVID-19 related articles, books, editorials, surveys etc. The number of citations served as the basis for all analyses. We analyzed annual trends, countries, institutions, authors, journals, keywords, and articles.

In 2021, the first year of the pandemic, there was a worldwide reduction in OHT and OLT transplant procedures due to multiple factors; In addition to the implementation of global lockdowns and travel restrictions that resulted in a decline in the incidence of serious injuries and accidents, which decreased the number of potential deceased donors[8,19]. During the first wave of the pandemic, there was a 4.5% decline in the number of donors dying from trauma, a 25% decline in donors dying from motor vehicle accidents, and a 35% upsurge in donors dying from substance addiction[20]. Furthermore, restrictions on acceptable donor criteria may have hampered organ referrals. In 2020, between 12% and 39% fewer donor referrals were reported[21,22]. Critical care staff workloads may also have made it more difficult to engage families in organ donation[23]. During the second year of the pandemic, COVID-19’s influence on transplant activity diminished although it was not eliminated[8]. Enormous breakthroughs were made in the management of COVID-19[24], innovative therapies were developed, and the vaccination of organ recipients was prioritized[9].

This decline in the number of transplantations was mirrored with a spike of the number of publications that discussed different topics related to the effect of the pandemic on this field. The number of publications was 139 in 2020; this figure more than doubled to 315 in 2021; and reached its peak of 379 articles in 2022.

The increase in publications from 2020 to 2023 signifies the global scientific community's urgent reaction to the COVID-19 pandemic, particularly in studies concerning heart and lung transplantation. The preeminence of studies from the United States, evidenced by the significant volume of publications and citations, indicates a robust research infrastructure and ample funding that facilitated the swift dissemination of new knowledge in this domain. The geographic distribution of research output may reflect the disparate impact of the pandemic across regions, necessitating a focused response from countries significantly affected by the virus in the early stages. Columbia University and Northwestern University, as leaders in citations, signify their crucial contribution to the advancement of transplantation knowledge during a global health crisis, likely impacting national and international guidelines and practices.

“Post-acute COVID-19 syndrome” published by Nalbandian et al[9] in Nature Medicine, which provided an in-depth investigation of the existing literature regarding post-acute COVID-19, its pathophysiology, and its organ-specific consequences, was the most cited study of all (n = 1357). With regards to journals, most publications were published in the Journal of Heart and Lung Transplantation (n = 101), followed by American Journal of Transplantation (n = 50), and Clinical Transplantation (n = 29).

The recurrent presence of the term "outcome" in the literature concerning heart and lung transplantation during the COVID-19 pandemic highlights its essential role in assessing the efficacy of medical interventions. This emphasis signifies a wider transition towards evidence-based medicine, wherein measurable outcomes are crucial for evaluating patient survival rates, quality of life, and the long-term efficacy of transplant procedures. The emphasis on outcomes related to COVID-19, alongside terms such as "immunosuppression", "extracorporeal membrane oxygenation", and "pulmonary fibrosis", underscores the interdisciplinary character of the research undertaken. These terms correspond with the clinical difficulties of managing immunosuppressed patients and individuals necessitating advanced respiratory assistance. The emergence of "vaccination" as a focal point towards the end of the study period indicates a transition to preventive measures, highlighting the evolving nature of research priorities in response to the ongoing challenges of the pandemic and advancements in treatment and prevention. This thorough emphasis facilitates continuous enhancements in clinical protocols and patient management strategies, guaranteeing that transplantation remains a feasible and efficacious treatment alternative despite the arduous circumstances presented by a global health crisis.

Bibliometric methods are a fundamental component of research evaluation methodology and are being utilized more frequently in the examination of a variety of scientific topics and in the ranking of institutions on a global scale[25]. In recent decades, digitization and online literature databases have assisted academics in evaluating literature and research performance due to ease of data access and navigation[26,27]. Despite the existence of numerous papers that address the bibliometric analysis of COVID-19 research, our bibliometric approach examining the impact of COVID-19 on OHT and OLT in depth is the first in the literature, this is inspired by our previously published bibliometric analysis investigating the effect of COVID-19 on abdominal organ transplant[28].

It is important to emphasize that this study is limited to articles retrieved from the Web of Science database, possibly omitting relevant studies from alternative sources. The limited search terms and dependence on citation counts to evaluate influence may introduce biases, as these metrics might not accurately represent the scientific rigor or interdisciplinary nature of the research. The exclusion of non-English studies might disregard important contributions from non-English speaking regions.

Despite these constraints, we believe that this study offers significant insights into the evolving research focus and identifies pivotal works in the domain of heart and lung transplantation during the COVID-19 pandemic, thereby directing future research trajectories and underscoring areas for additional investigation.

CONCLUSION

Our bibliometric analysis offers an in-depth overview of the research trends and academic works concerning the influence of COVID-19 on heart and lung transplantation. This study emphasizes the large volume of scientific literature generated during the pandemic. Through an analysis of publication patterns, prominent contributors, and areas of focused research, we provide valuable understanding of the changing landscape of transplantation research in relation to COVID-19. This highlights the significance of ongoing investigation and collaboration in this crucial field.