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Table of Contents
CASE REPORTS
Year : 2021  |  Volume : 5  |  Issue : 4  |  Page : 275-278

Challenges in management of severe COVID-19 in a post renal transplant patient co-infected with cytomegalovirus


1 Department of Anaesthesia and Intensive Care, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Cardiac Anaesthesia, U. N. Mehta Institute of Cardiology & Research Centre, Ahmedabad, Gujarat, India

Date of Submission16-Jul-2021
Date of Decision29-Sep-2021
Date of Acceptance05-Oct-2021
Date of Web Publication24-Nov-2021

Correspondence Address:
Dr. Guriqbal Singh
Department of Cardiac Anaesthesia, U. N. Mehta Institute of Cardiology and Research Center, Civil Hospital Campus, Asarwa, Ahmedabad 380016, Gujarat.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjoa.BJOA_78_21

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  Abstract 

Post-renal transplant patients are at higher risk of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infection due to suppressed immune system, underlying co-morbidities and antimetabolites used to prevent graft rejection. Cytomegalovirus infection causes memory inflation and further alters the clinical outcome. We report a case of severe COVID-19 in a post-renal transplant patient co-infected with cytomegalovirus and challenges in its management. The use of conventional protocol for treatment is a matter of concern in view of the complex clinical profile in them. Thus, it requires a multidisciplinary approach and individualization of the therapy to attain a fine balance between risk of graft rejection and complications of overimmunosuppression especially during cytokine storm. This brings us to explore other treatment modalities like cytosorb and plasmapheresis to prevent systemic inflammation in body while also targeting the cytomegalovirus infection.

Keywords: Cytomegalovirus, kidney transplantation, plasmapheresis, SARS-CoV-2


How to cite this article:
Rajamahanthi YP, Singh G. Challenges in management of severe COVID-19 in a post renal transplant patient co-infected with cytomegalovirus. Bali J Anaesthesiol 2021;5:275-8

How to cite this URL:
Rajamahanthi YP, Singh G. Challenges in management of severe COVID-19 in a post renal transplant patient co-infected with cytomegalovirus. Bali J Anaesthesiol [serial online] 2021 [cited 2021 Nov 28];5:275-8. Available from: https://www.bjoaonline.com/text.asp?2021/5/4/275/330958




  Introduction Top


Novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), was first identified and isolated in Wuhan, China, in December 2019. The Centers for Disease Control and Prevention (CDC) lists those requiring immunosuppression following renal transplantation, as high risk for severe disease from SARS-CoV-2.[1] We report about a patient who underwent deceased donor kidney transplant (DDKT) having cytomegalovirus (CMV) infection and presented with SARS-CoV-2. The use of conventional protocol presented several concerns because of the co-morbidities and required individualizing the treatment to balance the patient’s comorbidities and immunosuppressants especially during the cytokine storm.


  Case Report Top


A 60-year-old male patient who had been operated for DDKT secondary to end-stage renal disease was found to have CMV infection during his follow-up and was initiated on treatment with tab. ganciclovir. He was a known case of type 2 diabetes mellitus (DM), hypertension (HTN), and obstructive sleep apnea (OSA) for which he was on home Bilevel positive airway pressure (BiPAP) support. Patient presented with chief complaints of fever, generalized body pains, and tachypnoea for 5 days. In view of ongoing pandemic, he was evaluated for COVID-19 and nucleic acid test performed showed a positive result for SARS-Co-V-2. He was hemodynamically stable and had a temperature of 37.2°C, respiratory rate (RR) of 28/min, and oxygen saturation (SpO2) of 93% on room air. The patient was shifted to COVID intensive care unit (ICU) for further management. High resolution computed tomography (CT) scan of chest revealed COVID-19 reporting and data system (CORADS) score of 5 with CT severity score of 15/25. Oxygen was delivered using high flow nasal cannula for 2 h and ROX index score ([SpO2/FIO2]/RR) was 4, after which oxygen therapy was instituted with nasal- continuous positive airway pressure therapy (nCPAP). PaO2/FiO2 of patient was 73 after one hour of nCPAP ventilation with FiO2 of 100%. Lab values including interleukin-6 (IL-6), serum lactate dehydrogenase (LDH), C- reactive protein (CRP), D-dimer, Serum ferritin suggested ongoing cytokine storm on day 2 of admission [Table 1]. In view of adverse renal profile of drugs like remdesivir and favipiravir and risk of further immunosuppression by drugs like tocilizumab in this patient, decision was taken to subject this patient to cytosorb and plasmapheresis (PEX) therapy for the management of ongoing cytokine storm. Patient underwent cytosorb therapy for 48 h on days 6 and 7 and three sessions of PEX therapy on days 6, 7, and 10 of admission in ICU. Patient was also given three doses of intravenous immunoglobulins (IVIG). Post cytosorb and PEX therapy patient’s laboratory and clinical picture had improved significantly [Table 1]. The inflammatory markers and other lab values showed improvement on day 12 compared to day 2 [Table 1]. PaO2 had improved from 73 to 88 mm Hg on ABG post-therapy and chest X-ray showed improvement as well [Figure 1]. Clinically the respiratory distress had significantly improved, enabling the reduction of the ventilatory support [Table 2]. His treatment also included antibiotics as per culture and sensitivity, tacrolimus, mycophenolate mofetil, ganciclovir, heparin, and methylprednisolone. Patient was then weaned off CPAP and discharged with spO2 of 98% and RR 20/min. He was advised to use home BiPAP during the nights in view of OSA.
Table 1: Lab investigations of patients before and after Cytosorb and PEX therapy

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Figure 1: Chest X-ray showing diffuse opacification in bilateral lower zones on D2 and reduction in opacified area in bilateral lower zones suggestive of resolving consolidation on D12

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Table 2: Vitals and ventilatory parameters of patient from day 5 to day 11

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  Discussion Top


DDKT patients are at higher risk of SARS-CoV-2 infection due to suppressed immune system, CKD, underlying comorbidities like HTN, DM, and antimetabolites used to prevent graft rejection. CMV infection in post-transplant patients further alters the clinical outcome. It is associated with immune senescence by the phenomenon of memory inflation.[2] Attrition of these naïve T cell is detrimental as this suppresses immune response, reduces pathogen clearance, and increases viral shedding early during the clinical course of COVID illness.

Initially, conventional management of COVID-19 included use of convalescent plasma therapy (CPT), antiviral drugs such as remdesivir, favipiravir, and tocilizumab based on severity of the disease. Administration of CPT was not considered at his presentation due to history of recent DDKT and inconclusive data at that point in time given his clinical history. The only randomized clinical trial (RCT) available at the time indicated no changes or improvement in clinical symptoms.[3] Further, the pharmacokinetics and pharmacodynamics of remdesivir and favipiravir were unfavorable to a patient who underwent DDKT, 6 months ago. Grein et al.[4] had reported renal impairments, acute kidney injury and hematuria in 8, 6 and 4% of the remdesivir recipients, respectively. Also, favipiravir is eliminated by kidneys and clinical data is inadequate about its clearance by dialysis. Hence, the possibility of adverse events caused by its accumulation had to be considered.[5] A conscious decision was taken not to use antiviral drugs to target SARS-CoV-2. Treating the cytokine storm was important as it is associated with disease severity, leading to capillary leak syndrome, progressive lung injury, respiratory failure and acute respiratory distress syndrome (ARDS). Tocilizumab was in use to curb cytokine storm, but administration of tocilizumab would only add to superinfections in a patient with suppressed immune system, superimposed by CMV infection.[6] Thereby, cytosorb and PEX were used as an alternative approach. Cytosorb is an extracorporeal cytokine adsorber and hemadsorption with cytosorb can remove up to 90% of circulating endotoxins and cytokines.[7] Cytosorb cartridge was used when hemodialysis was performed to keep serum creatinine and urea under control. Likewise, PEX is also an extracorporeal treatment that selectively removes abnormal substances like IL-6 and IL-23, most notably larger molecules from the blood. SARS-CoV-2 has a diameter of 60—140 nm, also large enough to be eliminated. This is the main rationale for performing PEX therapy for critical patients with lung injury.[8],[9],[10] Simultaneously CMV viral load was targeted using ganciclovir and IVIG to prevent immune attrition. Both steroid and antimetabolites were continued, dosage of steroid was increased and that of antimetabolites were reduced. It is hypothesized that antimetabolites can lead to immune modulation against the virus and thus may be beneficial in reducing the cytokine release storm. Thus, cautious reduction rather than the complete elimination of immunosuppression may avoid precipitation of severe complications like ARDS.

Treating a post-renal transplant COVID positive patient requires careful tailoring of the therapy to suit individual patient’s profile. A balance between risk of graft rejection and complications of overimmunosuppression should be explored to avoid worsening of COVID-19 complications and superinfections. Hence, a dual approach was used, firstly to improve the condition of lung while preserving the transplanted kidney using PEX, cytosorb, and steroid therapy by foiling cytokine storm. Secondly, CMV was targeted using ganciclovir and IVIG to prevent immune senescence.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Johnson KM, Belfer JJ, Peterson GR, Boelkins MR, Dumkow LE. Managing COVID-19 in renal transplant recipients: A review of recent literature and case supporting corticosteroid-sparing immunosuppression. Pharmacotherapy 2020;40:517-24.  Back to cited text no. 1
    
2.
Moss P. “The ancient and the new”: Is there an interaction between cytomegalovirus and SARS-cov-2 infection? Immun Ageing 2020;17:14.  Back to cited text no. 2
    
3.
Bakhtawar N, Usman M, Khan MMU. Convalescent plasma therapy and its effects on COVID-19 patient outcomes: A systematic review of current literature. Cureus 2020;12:e9535.  Back to cited text no. 3
    
4.
Fan Q, Zhang B, Ma J, Zhang S. Safety profile of the antiviral drug remdesivir: An update. Biomed Pharmacother 2020;130:110532.  Back to cited text no. 4
    
5.
Koshi E, Saito S, Okazaki M, Toyama Y, Ishimoto T, Kosugi T, et al. Efficacy of favipiravir for an end stage renal disease patient on maintenance hemodialysis infected with novel coronavirus disease 2019. CEN Case Rep 2021;10:126-31.  Back to cited text no. 5
    
6.
Trujillo H, Caravaca-Fontán F, Sevillano Á, Gutiérrez E, Fernández-Ruiz M, López-Medrano F, et al. Tocilizumab use in kidney transplant patients with COVID-19. Clin Transplant 2020;34:e14072.  Back to cited text no. 6
    
7.
Alharthy A, Faqihi F, Memish ZA, Balhamar A, Nasim N, Shahzad A, et al. Continuous renal replacement therapy with the addition of cytosorb cartridge in critically ill patients with COVID-19 plus acute kidney injury: A case-series. Artif Organs 2021;45:E101-12.  Back to cited text no. 7
    
8.
Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021.  Back to cited text no. 8
    
9.
Wang Q, Hu Z. Successful recovery of severe COVID-19 with cytokine storm treating with extracorporeal blood purification. Int J Infect Dis 2020;96:618-20.  Back to cited text no. 9
    
10.
Gilmutdinova IR, Yakovlev MY, Eremin PS, Fesun AD. Prospects of plasmapheresis for patients with severe COVID-19. Eur J Transl Myol 2020;30:9165.  Back to cited text no. 10
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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