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Solid Organ Transplantation in the Era of COVID-19

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A special issue of Transplantology (ISSN 2673-3943). This special issue belongs to the section "Solid Organ Transplantation".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 31991

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Dr. Macé M. Schuurmans

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Guest Editor

Medical Director of Lung Transplant and adult Cystic Fibrosis Programme, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
Interests: lung transplantation; medical management; viral infections; chronic allograft dysfunction; cystic fibrosis and smoking cessation

Dr. René Hage

E-Mail Website
Guest Editor

Division of Pulmonology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
Interests: lung transplantation; cystic fibrosis; viral infections; immunosuppression; COVID-19 in lung transplant recipients

Special Issue Information

Dear Colleagues,

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), posing a new challenge to the medical care of solid organ transplant (SOT) recipients. Due to the relatively small number of studies in SOT recipients suffering from COVID-19, the natural course of the SARS-CoV-2 infection, optimal treatment strategies including modification of immunosuppressive therapy and the prognosis in COVID-19 in these patients is incompletely understood. Many SOT recipients have significant comorbidities, such as arterial hypertension, chronic renal failure, diabetes and obesity, which are also known risk factors for severe COVID-19. On the other side, preliminary data show a probable beneficial effect of immunosuppression in preventing or mitigating the hyperinflammation (cytokine storm syndrome) in severe COVID-19. In COVID-19, there remain many open questions, such as optimal treatment, the risk of transmitting SARS-CoV-2 from an organ donor to a recipient, the risk of SARS-CoV-2 positive health care providers, and how to manage patient fear that has led to patients canceling or delaying necessary planned ambulatory hospital visits. Ongoing studies will inform us whether or not vaccination can adequately protect SOT recipients, and if they also benefit from possible herd immunity in the general population.

The current Special Issue aims to fill some of the knowledge gaps and highlight some recent advances in the management of SOT patients during the pandemic. The present call for manuscripts is addressed to healthcare professionals involved in SOT patient care. We welcome comprehensive reviews, original studies, interesting case series or case reports and commentaries relating to this topic. It is important to know that submitted articles will be processed in a timely manner, and once accepted, they will be immediately published online without delay. This Special Issue will then be compiled once 6–8 articles have been accepted.

Dr. Macé M. Schuurmans
Dr. René Hage
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Transplantology is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Solid organ transplant
Transplantation
Viral infection
COVID-19
SARS-CoV-2

Published Papers (12 papers)

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Editorial

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4 pages, 211 KiB

Open AccessEditorial

COVID-19: Impact on Lung Transplant Activity at a Large Brazilian Hospital

by Mauro Razuk Filho, Lucas Matos Fernandes and Paulo Manuel Pêgo-Fernandes

Transplantology 2022, 3(2), 184-187; https://doi.org/10.3390/transplantology3020019 - 13 May 2022

Viewed by 1443

Abstract

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in late 2019, and has caused a huge number of hospitalizations and deaths worldwide [...] Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

Research

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8 pages, 249 KiB

Open AccessArticle

by René Hage and Macé M. Schuurmans

Transplantology 2022, 3(4), 275-282; https://doi.org/10.3390/transplantology3040028 - 23 Sep 2022

Viewed by 1705

Abstract

Introduction: We report on characteristics and lung function outcomes among lung transplant recipients (LTRs) after COVID-19 with infections occurring in the first year of the coronavirus pandemic prior to introduction of the vaccines. Methods: This was a retrospective study of 18 LTRs who tested positive for SARS-CoV-2 between 1 February 2020 and 1 March 2021. The mean age was 49.9 (22–68) years; 12 patients (67%) were male. Two patients died due to severe COVID-19. Results: During the study period, there were 18 lung transplant recipients with a community-acquired SARS-CoV-2 infection. In this cohort, seven had mild, nine had moderate, and two had severe COVID-19. All patients with mild and moderate COVID-19 survived, but the two patients with severe COVID-19 died in the intensive care unit while intubated and on mechanical ventilation. Most patients with moderate COVID-19 showed a permanent lung function decrease that did not improve after 12 months. Conclusion: A majority of LTRs in the current cohort did not experience an alteration in the trajectory of FEV1 evolution after developing SARS-CoV-2 infection. However, in the patients with moderate COVID-19, most patients had a decline in the FEV1 that was present after 1 month after recovery and did not improve or even deteriorated further after 12 months. In LTRs, COVID-19 can have long-lasting effects on pulmonary function. Treatment strategies that influence this trajectory are needed. Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

10 pages, 270 KiB

Open AccessArticle

Outcomes of COVID-19 in a Large Cohort of Lung Transplant Recipients: A Retrospective Study

by Domingo J. Franco-Palacios, Mei Lu, Mary Grace Fitzmaurice and George Alangaden

Transplantology 2022, 3(3), 257-266; https://doi.org/10.3390/transplantology3030026 - 22 Jul 2022

Cited by 1 | Viewed by 1818

Abstract

Background: Early reports of COVID-19 in lung transplant recipients (LTRs) showed high hospitalization and mortality rates. However, the outcomes of COVID-19 in LTRs since the advent of newer therapies and vaccines have been poorly defined. Methods: We evaluated the risks for SARS-CoV-2-related hospitalization and mortality in a cohort of LTRs at the Henry Ford Lung Transplant Program in Detroit, Michigan during the study period March 2020–March 2022. Univariate logistic regression, followed by multivariable modeling were performed to estimate the odds ratio (OR) with 95% confident intervals (CI). Results: Sixty-four laboratory-confirmed SARS-CoV-2 infections were identified in 59 patients. For the primary analysis of the hospitalization and mortality risks, we included these 59 patients with symptomatic COVID-19. SARS-CoV-2 infections were confirmed with real-time polymerase chain reaction (RT-PCR) from a nasopharynx swab. The mean age (±STD) was 61 (±12), 63% were males, 27% were African Americans, and the time from lung transplant to COVID-19 was 5.5 (±4.8) years. Thirty-four (57.6%) patients were hospitalized, and the inpatient mortality rate was 24% (8/34). A multivariable analysis showed that patients with a higher baseline forced expiratory volume (FEV1) were less likely to be hospitalized (OR = 0.91 and 95% CI 0.87–0.98, p = 0.02). Seventy-five percent (75%; 6/8) of patients on invasive mechanical ventilation died, compared with only 8% mortality rate in those without mechanical ventilation (OR = 36.0 and 95% CI 4.2–310.4, p < 0.01). Although a trend toward a higher risk of death was observed in those infected during the Alpha (p = 0.17) and Delta (p = 0.22) waves, no significant risk was detected after adjusting for other covariates. Five LTRs were diagnosed with COVID-19 twice. Thirty of the sixty-four COVID-19 cases (46.8%) occurred in LTRs that had received at least two doses of any of the available mRNA vaccines at a median of 123 days (IQR 98–164 days) after vaccination. Twelve of the thirty (40%) were hospitalized, and four patients (33%) died during their hospitalizations. Conclusions: In our LTR population, the hospitalization and mortality rates associated with COVID-19 were high despite the increased use of new therapies. Vaccine-breakthrough infections were common and were associated with poor outcomes. Studies are needed to determine optimal prevention and therapeutic strategies to improve COVID-19 outcomes in LTRs. Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

8 pages, 485 KiB

Open AccessArticle

SARS-CoV-2 Infection of Unvaccinated Liver- and Kidney-Transplant Recipients: A Single-Center Experience of 103 Consecutive Cases

by Hailey Hardgrave, Allison Wells, Joseph Nigh, Tamara Osborn, Garrett Klutts, Derek Krinock, Mary Katherine Rude, Sushma Bhusal, Lyle Burdine and Emmanouil Giorgakis

Transplantology 2022, 3(2), 200-207; https://doi.org/10.3390/transplantology3020021 - 16 Jun 2022

Cited by 1 | Viewed by 1742

Abstract

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was declared a pandemic in March 2020. Its reported impact on solid-organ-transplant-recipient morbidity and mortality has varied. The aim of this study was to present the effect of transplant status, patient comorbidities and immunosuppression modality on the survival of solid-organ-transplant recipients who contracted SAR-CoV-2 during the pre-vaccination era, at a single academic transplant center. Patients (n = 103) were assessed for 90-day mortality. A univariate analysis identified an age of over 60 years (HR = 10, p = 0.0034), Belatacept (HR = 6.1, p = 0.022), and Cyclosporine (HR = 6.1, p = 0.0089) as significant mortality risk factors; Tacrolimus was protective (HR = 0.23, p = 0.022). Common metabolic comorbidities (hypertension, diabetes, obesity) did not stand out as risk factors in our patient cohort. This study on the unvaccinated is expected to facilitate a paired comparison of outcomes in transplanted patients who contracted SARS-CoV-2 during the latter period of the pandemic, when broad SARS-CoV-2 vaccination and novel antibody treatments became broadly available. Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

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8 pages, 512 KiB

Open AccessCommunication

COVID-19 Severity and Mortality in Solid Organ Transplantation: Differences between Liver, Heart, and Kidney Recipients

by Ricardo Wesley Alberca, Gabriela Gama Freire Alberca, Lucas Chaves Netto, Raquel Leão Orfali, Sarah Cristina Gozzi-Silva, Alberto José da Silva Duarte, Valeria Aoki, Maria Notomi Sato and Gil Benard

Transplantology 2021, 2(3), 296-303; https://doi.org/10.3390/transplantology2030030 - 18 Aug 2021

Cited by 5 | Viewed by 3697

Abstract

The infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can generate a wide spectrum of clinical manifestations ranging from asymptomatic to severe respiratory and systemic disease with coagulation disorder named coronavirus disease 2019 (COVID-19). Patients with comorbidities have been identified as risk groups for severe COVID-19, also having a higher death risk. Previous reports have conflicting results regarding if solid organ transplant recipients present an increased risk for COVID-19. Nevertheless, previous investigations failed to distinguish between different organs received or made a longitudinal investigation on those patients. We recruited 39 solid organ transplant recipients: 25 kidney transplant recipients, 7 heart transplant recipients, and 7 liver transplant recipients and 25 age-matched non-transplant COVID-19 patients without comorbidities (control group) and compared daily laboratory data in addition to performing survival analysis. Heart and kidney transplant recipients presented an increase in several COVID-19 severity-associated biomarkers, such as neutrophil-to-lymphocyte ratio and thrombocytopenia, in comparison to the control group and liver transplant recipients. Heart and kidney transplant recipients also presented an increase in the need for intensive care and invasive mechanical ventilation during the disease’s course. Importantly, heart and kidney transplant recipients presented a higher mortality rate in comparison to liver transplant recipients and non-transplant recipients. In our cohort, heart and kidney transplant recipients presented a difference in clinical characteristics and survival rate in comparison to liver transplant recipients. Further investigation involving immune response to SARS-CoV-2 in solid organ recipients should consider and separate patients according to the organ grafted. Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

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Review

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11 pages, 300 KiB

Open AccessReview

COVID-19-Associated Lung Fibrosis: Two Pathways and Two Phenotypes, Lung Transplantation, and Antifibrotics

by René Hage and Macé M. Schuurmans

Transplantology 2022, 3(3), 230-240; https://doi.org/10.3390/transplantology3030024 - 06 Jul 2022

Cited by 1 | Viewed by 1971

Abstract

COVID-19 can be associated with lung fibrosis. Although lung fibrosis after COVID-19 is a relatively rare finding, the mere fact that globally a very large number of patients have had COVID-19 leads to a significant burden of disease. However, patients with COVID-19-associated lung fibrosis have different clinical and radiological features. The aim of this review is to define the different phenotypes of COVID-19-associated lung fibrosis, based on the medical literature. We found that two phenotypes have emerged. One phenotype is COVID-19-related acute respiratory distress syndrome (CARDS); the other phenotype is post-COVID-19 pulmonary fibrosis (PCPF). Both phenotypes have different risk factors, clinical, and radiological features, and differ in their pathophysiological mechanisms and prognoses. A long-term follow-up of patients with pulmonary complications after COVID-19 is warranted, even in patients with only discrete fibrosis. Further studies are needed to determine the optimal treatment because currently the literature is scarce, and evidence is only based on small case series or case reports. Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

14 pages, 559 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Transplant Drugs against SARS, MERS and COVID-19

by René Hage, Carolin Steinack, Fiorenza Gautschi and Macé M. Schuurmans

Transplantology 2020, 1(2), 71-84; https://doi.org/10.3390/transplantology1020007 - 03 Oct 2020

Cited by 4 | Viewed by 3305

Abstract

There is an urgent need to develop drugs and vaccines to counteract the effects of the new coronavirus SARS-CoV-2 and adequately treat the corona virus disease (COVID-19). As these drugs are still under investigation, research also focuses on existing medication with proven effectiveness in other coronaviral diseases. The advantages of existing therapeutic drugs that are currently approved (for other indications) are the known safety profile, general availability and relatively lower costs involved in extending the purpose to a new disease. Calcineurin inhibitors (CNI) are drugs that have shown effectiveness in several coronaviral diseases, and are well-known and widely used drugs in transplant medicine. The aim of this narrative review is to present the current evidence of CNI in coronaviral diseases, the biophysiology of CNI and to suggest possible ways to study CNI as a new treatment option for COVID-19. We searched original papers, observational studies, case reports, and meta-analyses published between 2000 and 2020 in English in the PubMed database and Google Scholar using the keywords: (coronavirus), (treatment), (MERS), (SARS), (COVID-19), (tacrolimus), (ciclosporin), (cyclosporin) AND (calcineurin inhibitor). We excluded studies in patients with clear indications for immunosuppressive therapy. Additionally, we searched in the preprint servers and the World Health Organization bulletin. Ten studies were identified and included. Calcineurin inhibitor therapy has been suggested to be effective for coronaviral diseases in different settings. The results are summarized in a table. CNI should be investigated as a first treatment option based on evidence of direct antiviral effects and its properties preventing severe systemic hyperinflammation, as has been observed in COVID-19 with predominantly pulmonary immunopathological changes. Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

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15 pages, 875 KiB

Open AccessFeature PaperEditor’s ChoiceReview

COVID-19 in Patients with Solid Organ Transplantation: A Systematic Review

by René Hage, Carolin Steinack, Christian Benden and Macé M. Schuurmans

Transplantology 2020, 1(1), 1-15; https://doi.org/10.3390/transplantology1010001 - 07 May 2020

Cited by 18 | Viewed by 4765

Abstract

The novel coronavirus, SARS-CoV-2, is causing a pandemic of unknown precedent, with huge healthcare challenges and worldwide disruptions to economic and social life. Lung transplant recipients and other solid organ transplant (SOT) recipients are immunosuppressed, and therefore are generally considered at an increased risk for severe infections. Given the current gap in knowledge and evidence regarding the best management of these patients, we conducted a systematic review of studies on SARS-CoV-2 infections and Coronavirus Disease 2019 (COVID-19) in SOT recipients, to evaluate the association between immunosuppression in these patients, SARS-CoV-2 infection and COVID-19 outcomes. The focus was the severity of the disease, the need for mechanical ventilation and intensive care unit (ICU) admissions, and rate of death. The literature search was conducted repeatedly between 16 March and 8 April 2020. We searched original papers, observational studies, case reports, and meta-analyses published between 2019 and 2020 using two databases (PubMed, Google Scholar) with the search terms: [transplant OR immunosuppression] AND [COVID-19 OR SARS-CoV-2]. Further inclusion criteria were publications in English, French, German and Italian, and reference to humans. We also searched the reference lists of the studies encountered. From an initial search of PubMed and Google Scholar, 19 potential articles were retrieved, of which 14 were excluded after full-text screening (not being case reports or case series), leaving 5 studies for inclusion. No further studies were identified from the bibliographies of retrieved articles. Based on the limited research, no firm conclusions can be made concerning SOT recipients, but the current evidence suggests that immunosuppression is most likely associated with a better outcome of SARS-CoV-2 infection and COVID-19 because it prevents hyperinflammation (cytokine storm) in this particular population. There is a need for further research that would allow results to be adjusted for other factors potentially impacting COVID-19 severity and outcome. Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

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Other

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3 pages, 204 KiB

Open AccessBrief Report

Effect of Remdesivir on COVID-19 PCR Positivity and Cycle Threshold in Kidney Transplant Recipients

by Ryan J. Winstead, Johanna Christensen, Sara Sterling, Megan Morales, Dhiren Kumar, Alexandra Bryson and Gaurav Gupta

Transplantology 2021, 2(3), 291-293; https://doi.org/10.3390/transplantology2030028 - 18 Aug 2021

Cited by 3 | Viewed by 2572

Abstract

Information regarding Coronavirus disease 2019 in the transplant population is lacking. Recently it has been suggested that cycle threshold values obtained on polymerase chain reaction tests may serve as a marker of disease severity with lower values (i.e., higher viral load) being associated with higher mortality. This study was done to assess the impact of remdesivir use on the time to a negative COVID-19 PCR as well as the degree of change between two Ct’s based on treatment. A total of 30 kidney transplant patients with a new diagnosis of COVID-19 were assessed. Serial PCR results were followed from the time of diagnosis then every 2–4 weeks until negative. In patients who received remdesivir immediately after COVID-19 confirmation compared to no remdesivir, time to negative PCR was not statistically different with a median duration of 57 days in both groups (p = 0.369). The change in the Ct between the first and the second PCR test was also not statistically different between groups with a median change of 18.4 cycles in the remdesivir group and 15.7 cycles without remdesivir (p = 0.516). The results of this small single-center analysis suggest that remdesivir may not be beneficial in shortening time to a negative COVID-19 PCR. Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

17 pages, 691 KiB

Open AccessCase Report

Clinical Characteristics, Treatments and Outcomes of 18 Lung Transplant Recipients with COVID-19

by René Hage, Carolin Steinack, Fiorenza Gautschi, Susan Pfister, Ilhan Inci and Macé M. Schuurmans

Transplantology 2021, 2(2), 229-245; https://doi.org/10.3390/transplantology2020022 - 15 Jun 2021

Cited by 5 | Viewed by 2853

Abstract

We report clinical features, treatments and outcomes in 18 lung transplant recipients with laboratory confirmed SARS-CoV-2 infection. We performed a single center, retrospective case series study of lung transplant recipients, who tested positive for SARS-CoV-2 between 1 February 2020 and 1 March 2021. Clinical, laboratory and radiology findingswere obtained. Treatment regimens and patient outcome data were obtained by reviewing the electronic medical record. Mean age was 49.9 (22–68) years, and twelve (67%) patients were male. The most common symptoms were fever (n = 9, 50%), nausea/vomiting (n = 7, 39%), cough (n = 6, 33%), dyspnea (n = 6, 33%) and fatigue (n = 6, 33%). Headache was reported by five patients (28%). The most notable laboratory findings were elevated levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH). Computed Tomography (CT) of the chest was performed in all hospitalized patients (n = 11, 7%), and showed ground-glass opacities (GGO) in 11 patients (100%), of whom nine (82%) had GGO combined with pulmonary consolidations. Six (33%) patients received remdesivir, five (28%) intravenous dexamethasone either alone or in combination with remdesivir, and 15 (83%) were treated with broad spectrum antibiotics including co-amoxicillin, tazobactam-piperacillin and meropenem. Four (22%) patients were transferred to the intensive care unit, two patients (11%) required invasive mechanical ventilation who could not be successfully extubated and died. Eighty-nine percent of our patients survived COVID-19 and were cured. Two patients with severe COVID-19 did not survive. Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

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5 pages, 1671 KiB

Open AccessCase Report

Presentation of SARS-CoV-2 in a Pediatric Heart Transplant Recipient with Multiple Underlying Comorbidities

by Bibhuti B. Das

Transplantology 2021, 2(1), 87-91; https://doi.org/10.3390/transplantology2010009 - 22 Mar 2021

Cited by 1 | Viewed by 2136

Abstract

A six-year-old heart transplant recipient with additional significant co-morbidities, including severe hypoxic-ischemic injury, gastrostomy, tracheostomy, and mechanical ventilation dependency, encountered SARS-CoV-2 infection. The patient received tacrolimus and mycophenolate to prevent graft rejection, presented initially with SARS-CoV-2 positive and presumed pseudomonas aeruginosa pneumonia. Twenty-three days later, the patient presented with fever recurrence with evidence for systemic inflammation, which resolved rapidly with high-dose methylprednisolone. Interestingly, while IgM to SARS-CoV-2 was present, IgG was not detected even three months after his first positive test for SARS-CoV-2. The author discusses potential immune mechanisms that might have affected the course of multi-system inflammatory syndrome children (MIS-C) in this patient. Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

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8 pages, 1342 KiB

Open AccessFeature PaperEditor’s ChoiceCase Report

SARS-CoV-2 and Norovirus Co-Infection after Lung Transplantation

by Carolin Steinack, René Hage, Christian Benden and Macé M. Schuurmans

Transplantology 2020, 1(1), 16-23; https://doi.org/10.3390/transplantology1010002 - 29 May 2020

Cited by 3 | Viewed by 2805

Abstract

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spreading as a pandemic in 2020. Few reports on infections in thoracic transplantation have been published so far. We present a case of COVID-19 in a 55-year old female lung transplant recipient infected 5 months posttransplant, who additionally was co-infected with a Norovirus. Respiratory and gastrointestinal symptoms were observed without need of therapeutic escalation except for antibiotic therapy. We observed a moderate disease evolution likely due to triple immunosuppression. Full article

(This article belongs to the Special Issue Solid Organ Transplantation in the Era of COVID-19)

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