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Volume: 19 Issue: 9 September 2021

FULL TEXT

REVIEW
Impact of COVID-19 Pandemic on Management of Pediatric Kidney Transplant Recipients

Abstract

Children appear to be less commonly and less severely affected by COVID-19 than adults, accounting for 1% to 5% of all COVID-19 cases. The COVID-19 pande­mic has challenged pediatric kidney transplant programs to provide safe and consistent care during this difficult and unprecedented time. So far during this pandemic, best practices being delivered to pediatric kidney transplant patients are based on available information from published literature and expert opinions. The key areas of pediatric kidney transplant care that may be affected by the COVID-19 pandemic include transplant activity, outpatient clinic activity, monitoring, multidisciplinary care, medications (immunosuppression and others), patient/family education/support, school and employment, and care of pediatric kidney transplant patients who are COVID-19 positive. It has been presumed that children with chronic kidney disease and/or those who take immunosuppressants may be at increased risk for complications from COVID-19 infection; however, available evidence has now suggested that immunosuppressed children with kidney transplant are not at increased risk of severe COVID-19 disease. Clinicians should remain aware that transplant recipients may present with atypical symptoms. In addition, because evidence-based reports to support specific adjustments to immunosuppressive medi­cations in relation to COVID-19 are not yet available, decisions on reduction or discontinuation of immuno­suppression should be on a case-by-case basis for kidney transplant recipients who are COVID-19 positive. Reports to support evidence-based mana­gement of pediatric kidney transplant patients during the COVID-19 pandemic are lacking; therefore, expert opinion and available knowledge and experience remain subject to biases.


Key words : Coronavirus disease 2019, Pediatric nephrology, Renal transplantation, Severe acute respiratory syndrome coronavirus 2

Introduction

As of March 2, 2021, over 115 million cases of COVID-19 have been reported globally.1 Children appear to be less commonly and less severely affected than adults, accounting for 1% to 5% of all COVID-19 cases and 0% to 1% of reported fatalities.2,3

In December 2020, news media reported a new variant of the coronavirus that causes COVID-19; since then, other variants have been identified and are under investigation. One of the many questions raised by the new variants was whether a new COVID-19 variant could affect children more frequently than earlier strains. In a recent COVID-19 update from the Johns Hopkins Medicine Website, featured experts in SARS-CoV-2 talked about what is known about these new variants and mentioned that there is no convincing evidence that any of the variants have special propensity to infect or cause disease in children.4 The COVID-19 pandemic has challenged pediatric kidney transplant (PKT) programs to provide safe and consistent care during this difficult and unprecedented time. To date, national and international transplant societies have provided general guidance and recommendations for management of care in transplant programs and delivery of patient care during the COVID-19 pandemic. Only a few of these recommendations are specific to pediatric patients.5 Best practices being delivered to pediatric kidney transplant patients are so far based on available information from published literature, expert opinions, international kidney transplant and or organ procurement societies/­agencies, and Webinars. Data on COVID-19 are rapidly evolving; therefore, these practices may need to be revised as new knowledge emerges.

The Challenge of the COVID-19 Pandemic on Pediatric Kidney Transplant Recipients
The COVID-19 pandemic has challenged PKT programs to provide safe and consistent care. Although data are still emerging, it has been presumed that children with chronic kidney disease and/or those who take immunosuppressants may be at increased risk of complications from COVID-19 infection. The implementation of necessary public health measures, such as physical distancing, school and childcare closures, and restrictions on hospital services, has impacted the ways that health care providers deliver care to PKT patients.

The identified challenges during the COVID-19 pandemic include the following: supply and disruption of medications, especially immunosup­pressive medications; challenges with virtual visits; lack of technology/infrastructure to support telehealth; the need for reorganization of clinic infrastructure and resources to meet with demands of maintaining a low-risk environment for in-person visits; patient anxiety and fear of contracting COVID-19 during clinic visits and/or during visits for follow-up laboratory studies, leading to suboptimal monitoring and/or late presentation with comp­lications; lack of established knowledge to make informed decisions on immunosuppression mana­gement; and the lack of knowledge of risks and effects of COVID-19 in the PKT population. However, there are several identified successes, such as the ability to continue delivering patient care in a rapidly changing environment; the ability to provide timely communications with patients and families in a rapidly changing environment; the lack of international publications reporting significant complications in PKT patients diagnosed with COVID-19; the ability to quickly share evolving clinical experiences and knowledge with PKT professionals and to develop current consensus guidance on management of PKT patients during the COVID-19 pandemic; and the ability to partner with other organ groups, adult care colleagues, and international colleagues to gather and respond to the best available evidence.

The key areas of PKT care that may be affected by the COVID-19 pandemic are as follows: transplant activity, outpatient clinic activity, monitoring, multi­disciplinary care, medications (immunosuppressants and others), patient/family education/support, school and employment, and management of PKT patients who are COVID-19 positive.

With regard to lack of significant complications reported in PKT patients diagnosed with COVID-19, in Canada, for example, of 101 019 cases of COVID-19 that have been reported, 6.97% were children ≤19 years of age, accounting for 1% of hospitalized patients, and 1% of these patients were admitted to intensive care with no reported fatalities.6

Pediatric kidney transplant should be considered an emergent or urgent life-saving procedure and be given priority. Nevertheless, in the early stages of the pandemic, many programs suspended both preemptive and living donor kidney transplant procedures and limited deceased donor transplants to those with the highest need. No programs accepted donors or recipients who were confirmed to be COVID-19 positive, acknowledging that the risk of transmission of the virus through donor organs had not been established.5

In this regard, ongoing national and global collaborations are needed to develop a unified approach to suspension and resumption of kidney transplant activities at each center. The approach should be based on careful consideration of risks versus benefits of transplant based on certain considerations, especially with regard to degree of community spread and active cases of COVID-19 locally, the availability of rapid and accurate COVID-19 testing, and the availability of hospital and health care system capacity.

Although the COVID-19 pandemic started more than 1 year ago, data on PKT recipients remain limited; however, emerging and anecdotal reports have suggested that children follow a relatively mild course of COVID-19 and have better outcomes than adults.2,3,7 The incidence of COVID-19 in PKT recipients is similar to the general pediatric population.8 Therefore, immunosuppressed children with kidney transplant are not at increased risk of severe COVID-19 disease.9

The Canadian Society of Transplantation Pediatric Group has recently issued guidance on the management of PKT patients during the COVID-19 pandemic.5 This guidance recommended the following: only COVID-19 polymerase chain reaction test-negative donor and recipient pairs should proceed to transplant and, when possible, living donor and recipient pairs must self-isolate for 14 days leading up to the planned transplant surgery; all potential recipients must be informed at the time of organ offer of the potential risk of contracting COVID-19; all health care professionals must use appropriate personal protective equipment and health authorities must ensure that sufficient personal protective equipment is available to these providers; asymptomatic PKT patients should not be tested for COVID-19, unless required in advance of admission or procedure; and kidney allograft biopsies should be perfor­med as clinically indicated (graft dysfunction); otherwise, protocol biopsies should be deferred as allowed based on clinical status.

Many countries have closed schools and daycare facilities as a physical distancing measure. Children and young adolescents have been shown to be less susceptible to SARS-CoV-2, suggesting their relatively smaller role in transmission of the virus.10 Interestingly, school closure alone was reported to prevent 2% to 4% of deaths from COVID-19.11

Management of Pediatric Kidney Transplant Patients Who Are COVID-19 Positive
As a general principle, patients with suspected or confirmed COVID-19 must be isolated appropriately within a specific unit, and it is recommended that clinical care decisions for patients be assessed on a case-by-case basis and in consultation with a multidisciplinary care team with relevant expertise.5 However, most pediatric patients have mild symptoms and may not require admission.12

Currently available evidence has suggested that immunosuppressed PKT recipients are not at increased risk of severe COVID-19 disease.13 However, clinicians should be aware that transplant recipients may present with atypical symptoms, and thus clinicians should have a high level of suspicion. These symptoms include gastrointestinal symptoms, dermatologic manifestations (eg, chilblains, vasculitic rash), and pediatric inflammatory multisystem syndrome.14

Immunosuppression Management
There are currently no evidence-based reports to support specific adjustments to immunosuppressive medications in relation to COVID-19.15 Therefore, decisions about reduction or discontinuation of immunosuppression for kidney transplant recipients who are COVID-19 positive should be considered on a case-by-case basis along with close clinical assessment and consideration of the overall degree of immunosuppression after consultation with local infectious disease experts.

In mild to moderate cases, an initial reduction or discontinuation of antiproli­ferative agents (mycophenolate mofetil or azathioprine) should be considered. In moderate to severe cases or if there is progressive clinical deterioration, reduction or discontinuation of calcineurin inhibitors (CNI; tacrolimus or cyclosporine) should be considered. If immunosuppression is reduced or discontinued, the decision on when to resume administration should be considered on a case-by-case basis and upon clinical assessment of recovery of symptoms in consultation with local infectious disease experts.5

In contrast to adult populations, there is limited evidence on immunosuppressed children with kidney transplant, with the suggestion that children are not at increased risk of severe COVID-19 disease.8,9,13,16 Therefore, the degree of immunosuppression required should be determined on a case-by-case basis to avoid under- or overimmunosuppression.5

Lymphocyte-depleting induction agents should be avoided, as lymphopenia in COVID-19 patients is associated with severe disease.17 This would translate to the avoidance of “high-risk” transplant procedures if they can be safely deferred. These considerations remain at the discretion of the clinician and the individual transplant program. However, further studies are required to definitively ascertain these risks.

The suggestion for continuation of CNIs unless patients develop moderate-to-severe or progressively worsening COVID-19 is based on in vitro evidence, which suggests that Coronaviridae replication may require intact immunophilin pathways and that CNIs inhibit coronavirus replication.18

Renin-Angiotensin-Aldosterone System Inhibition and COVID-19 Disease
There has been much speculation of a possible association between severe COVID-19 disease and the use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers. However, the relationship is complex and not completely understood; nevertheless, the current evidence suggests that renin-angiotensin-aldosterone system inhibition does not facilitate SARS-CoV-2 infection and/or more severe COVID-19 disease. Therefore, The European Society of Hypertension has recently issued a statement on hypertension, renin-angiotensin system blockers, and COVID-19 in which the group suggested that angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers should not be routinely discontinued due to COVID-19. Moreover, any decisions to initiate or discontinue these medications should be subject to careful medical considerations led by the patient’s physician.18,19

Consideration for Antiviral Agents
Currently, there is no definitive evidence to support the efficacy of antiviral agents for treatment of COVID-19 in PKT recipients. If antiviral treatment is used, patients should have close monitoring for potential adverse outcomes and therapeutic drug levels due to possible drug-drug interactions. Preliminary results from a double-blind, randomized, placebo-controlled trial have suggested that intra­venous remdesivir may be effective in shortening the time to recovery in adults hospitalized with COVID-19, although no adult or PKT recipients were included.20

Consideration for Corticosteroids
The World Health Organization has recommended systemic corticosteroids in adults with severe COVID-19 because it was shown to reduce mortality.21 In contrast, systemic corticosteroid use was found to potentially increase the risk of death in patients without severe COVID-19.21

Systemic corticosteroids may be associated with prolonged viral shedding in the immunocom­promised host.22 The aforementioned guidance of the Canadian Society of Transplantation pediatric group has suggested systemic corticosteroid use in consultation with the intensive care team in patients with severe COVID-19, if there is progressive clinical deterioration, or if patients require ventilatory support.

Consideration for Convalescent Plasma
A Cochrane systematic review failed to confirm the efficacy of convalescent plasma in treatment of patients with COVID-19. Currently, there is no evidence to support the use of convalescent plasma in the treatment of COVID-19 in PKT recipients.23

Johns Hopkins Medicine researchers have studied the reaction of nearly 200 solid-organ transplant recipients to their first COVID-19 vaccine shot. They suggested that the Moderna and Pfizer/BioNTech mRNA vaccines can be safely given to this immunocompromised population.24

Conclusions

There is a paucity of literature to support evidence-based management of PKT patients during the COVID-19 pandemic. The expert opinions and available knowledge and experiences that are available are subject to biases associated with this level of evidence.


References:

  1. Worldometer. COVID-19 Coronavirus Pandemic. Accessed April 27, 2021. https://www.worldometers.info/coronavirus/
    CrossRef - PubMed
  2. Lu X, Zhang L, Du H, et al. SARS-CoV-2 infection in children. N Engl J Med. 2020;382(17):1663-1665. doi:10.1056/NEJMc2005073
    CrossRef - PubMed
  3. Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr. 2020;109(6):1088-1095. doi:10.1111/apa.15270
    CrossRef - PubMed
  4. Bollinger R, Ray S. The Johns Hopkins University. New Variants of Coronavirus: What You Should Know. https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/a-new-strain-of-coronavirus-what-you-should-know
    CrossRef - PubMed
  5. Teoh CW, Gaudreault-Tremblay MM, Blydt-Hansen TD, et al. Management of pediatric kidney transplant patients during the COVID-19 pandemic: guidance from the Canadian Society of Transplantation Pediatric Group. Can J Kidney Health Dis. 2020;7:2054358120967845. doi:10.1177/2054358120967845
    CrossRef - PubMed
  6. Government of Canada. Coronavirus disease 2019 (COVID-19): epidemiology update 2020. Accessed October 15, 2020. https://health-infobase.canada.ca/covid-19/epidemiological-summary-covid-19-cases.html
    CrossRef - PubMed
  7. Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in China. Pediatrics. 2020;145(6)e20200702. doi:10.1542/peds.2020-0702
    CrossRef - PubMed
  8. Marlais M, Wlodkowski T, Vivarelli M, et al. The severity of COVID-19 in children on immunosuppressive medication. Lancet Child Adolesc Health. 2020;4(7):e17-e18. doi:10.1016/S2352-4642(20)30145-0
    CrossRef - PubMed
  9. Minotti C, Tirelli F, Barbieri E, Giaquinto C, Dona D. How is immunosuppressive status affecting children and adults in SARS-CoV-2 infection? A systematic review. J Infect. 2020;81(1):e61-e66. doi:10.1016/j.jinf.2020.04.026
    CrossRef - PubMed
  10. Viner RM, Mytton OT, Bonell C, et al. Susceptibility to SARS-CoV-2 infection amongst children and adolescents compared with adults: a systematic review and meta-analysis. medRxiv. 2020;10.1101/2020.05.20.20108126:2020.2005.2020.20108126. doi:10.1101/2020.05.20.20108126
    CrossRef - PubMed
  11. Viner RM, Russell SJ, Croker H, et al. School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review. Lancet Child Adolesc Health. 2020;4(5):397-404. doi:10.1016/S2352-4642(20)30095-X
    CrossRef - PubMed
  12. CDC Covid-Response Team. Coronavirus disease 2019 in children - United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(14):422-426. doi:10.15585/mmwr.mm6914e4
    CrossRef - PubMed
  13. Bush R, Johns F, Acharya R, Upadhyay K. Mild COVID-19 in a pediatric renal transplant recipient. Am J Transplant. 2020;20(10):2942-2945. doi:10.1111/ajt.16003
    CrossRef - PubMed
  14. Guillen E, Pineiro GJ, Revuelta I, et al. Case report of COVID-19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation? Am J Transplant. 2020;20(7):1875-1878. doi:10.1111/ajt.15874
    CrossRef - PubMed

  15. Maggiore U, Abramowicz D, Crespo M, et al. How should I manage immunosuppression in a kidney transplant patient with COVID-19? An ERA-EDTA DESCARTES expert opinion. Nephrol Dial Transplant. 2020;35(6):899-904. doi:10.1093/ndt/gfaa130
    CrossRef - PubMed
  16. Fernandez-Ruiz M, Andres A, Loinaz C, et al. COVID-19 in solid organ transplant recipients: A single-center case series from Spain. Am J Transplant. 2020;20(7):1849-1858. doi:10.1111/ajt.15929
    CrossRef - PubMed
  17. Wu C, Chen X, Cai Y, et al. Risk Factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934-943. doi:10.1001/jamainternmed.2020.0994
    CrossRef - PubMed
  18. Willicombe M, Thomas D, McAdoo S. COVID-19 and calcineurin inhibitors: should they get left out in the storm? J Am Soc Nephrol. 2020;31(6):1145-1146. doi:10.1681/ASN.2020030348
    CrossRef - PubMed
  19. European Society of Hypertension. Statement of the European Society of Hypertension (ESH) on hypertension, renin-angiotensin system (RAS) blockers and COVID-19. 2020; https://www.eshonline.org/esh-content/uploads/2020/06/Statement-ESH-on-Hypertension-RAS-Blockers-and-COVID-19-Update-April-15-2020.pdf.
    CrossRef - PubMed
  20. Beigel JH, Tomashek KM, Dodd LE. Remdesivir for the treatment of Covid-19 - preliminary report. Reply. N Engl J Med. 2020;383(10):994. doi:10.1056/NEJMc2022236
    CrossRef - PubMed
  21. Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020;370:m3379. doi:10.1136/bmj.m3379
    CrossRef - PubMed
  22. Ogimi C, Greninger AL, Waghmare AA, et al. Prolonged shedding of human coronavirus in hematopoietic cell transplant recipients: risk factors and viral genome evolution. J Infect Dis. 2017;216(2):203-209. doi:10.1093/infdis/jix264
    CrossRef - PubMed
  23. Piechotta V, Chai KL, Valk SJ, et al. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2020;7(7):CD013600. doi:10.1002/14651858.CD013600.pub2
    CrossRef - PubMed
  24. Arthur R. Organ transplant patients can safely receive COVID-19 vaccine, says study. Available at https://www.biopharma-reporter.com/Article/2021/02/09/Organ-transplant-patients-can-safely-receive-COVID-19-vaccine-says-study. BioPharma Reporter.com. 2021.
    CrossRef - PubMed


Volume : 19
Issue : 9
Pages : 894 - 898
DOI : 10.6002/ect.2021.0275


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From the Farah Association for Child with Kidney Disease in Syria, Damascus, Syria
Acknowledgements: The author has not received any funding or grants in support of the presented research or for the preparation of this work and has no declarations of potential conflicts of interest.
Corresponding author: Bassam Saeed, PO Box 8292, Damascus, Syria
Phone: +963 11 3340766
E-mail: bmsaeed2000@yahoo.com