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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 4  |  Page : 361-365

COVID-19 infection in kidney transplant recipients during the first versus the second wave - Retrospective Observational study from a single center


1 Department of Nephrology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Critical Care Medicine, King George Medical University, Lucknow, Uttar Pradesh, India
3 Department of Urology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Submission16-Dec-2021
Date of Acceptance27-Oct-2022
Date of Web Publication30-Dec-2022

Correspondence Address:
Dr. Namrata S Rao
Department of Nephrology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_133_21

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  Abstract 


Background: Kidney transplant recipients (KTRs) are deemed to be at a high risk of severe coronavirus disease (COVID-19). Herein, we describe the clinical, laboratory profiles, management, and outcomes of 26 KTRs who developed COVID-19 during the first and second waves of the pandemic from a tertiary care center in northern India. Methods: This retrospective observational study included KTRs detected with COVID-19 infection during the first wave (March–November 2020) and the second wave (March–July 2021). Their clinical and laboratory investigations, management aspects, and outcomes were compared, using data retrieved from clinical and telenephrology records, and the hospital information system. Results: Of the 23 KTRs, 20 were male (86%), 20 patients had fever (86%), and cough and breathlessness were seen in 19 (82%) and 12 (52%), respectively. Acute graft dysfunction was seen in 6 (26%) patients, and the need for renal replacement was seen in 4 (17%) patients. Supplemental oxygen by reservoir mask was utilized in 10 (43%) patients, high-flow nasal cannula in 3 (13%), noninvasive mechanical ventilation in 4 (17%), and invasive mechanical ventilation in 6 (26%) patients. All the KTRs with moderate and severe COVID illness and 6/7 nonsurvivors were infected during the second wave. Overall mortality in this group of patients was very high at 27%, and the mortality in the group on mechanical ventilation was 100%. Conclusions: The second wave of the COVID-19 pandemic was associated with greater severity of illness and high mortality in KTRs.

Keywords: COVID-19, kidney, transplant


How to cite this article:
Rao NS, Chandra A, Saran S, Singh AK, Singh SK. COVID-19 infection in kidney transplant recipients during the first versus the second wave - Retrospective Observational study from a single center. Indian J Transplant 2022;16:361-5

How to cite this URL:
Rao NS, Chandra A, Saran S, Singh AK, Singh SK. COVID-19 infection in kidney transplant recipients during the first versus the second wave - Retrospective Observational study from a single center. Indian J Transplant [serial online] 2022 [cited 2023 Feb 8];16:361-5. Available from: https://www.ijtonline.in/text.asp?2022/16/4/361/364612




  Introduction Top


Coronavirus disease (COVID-19) started as a severe pneumonia of unknown cause in late 2019 and spread worldwide by early 2020. COVID-19 is predominantly a respiratory disease, but in severe cases, it can cause acute kidney injury and multiorgan failure. Kidney transplant recipients (KTRs) are at a high risk of developing severe COVID illness attributable to several risk factors, both transplant-specific (induction and antirejection therapies) and other comorbid conditions (underlying chronic kidney disease, diabetes mellitus, obesity, and hypertension).[1] In India, the period from March 2020 to November 2020 constituted the “first wave” and the period from March 2021 to July 2021 was referred to as the “second wave.” The second wave in India has been largely attributed to the coronavirus variant B.1.617.[2] Several case series and observational studies describe experiences from regional transplant centers worldwide with reported mortality rates of 8%–35% among KTRs, much higher than in the general population.[3],[4],[5] In our center, we noted a serious increase in mortality during the second wave, when compared to the first. This retrospective study compares the characteristics of hospitalized KTRs with COVID-19 infection during the first and second waves at a single center.


  Methods Top


This was a single-center retrospective observational study carried out in a tertiary care teaching hospital in northern India.

Inclusion criteria:

  1. Patients who underwent kidney transplant at our center (or followed up at our center within 1 month of transplant) and were diagnosed and hospitalized with COVID-19 infection at our center
  2. The period between March and October 2020 was considered the first wave, and the period between March and June 2021 constituted the second wave.


Exclusion criteria:

  1. Only telephonic follow-ups and telenephrology consults were excluded from the study
  2. Cases in which follow-up clinical and laboratory information could not be retrieved.


A total of 26 KTRs were diagnosed and hospitalized with COVID-19 infection (seven during the first wave, and 19 in the second wave). Of these, complete clinical and relevant laboratory details were available for 23 KTRs and were included in the study. Data were collected using the hospital information system and clinical records were filled after telenephrology consultations. The severity of COVID-19 illness in these patients was categorized on the basis of the COVID management protocol published by the Ministry of Health and Family Welfare (MOHFW), into mild, moderate, and severe.[6] During the first wave, all KTRs detected to be positive for SARS-CoV2 reverse transcription–polymerase chain reaction were hospitalized. However, during the second wave, COVID-positive KTRs were all assessed initially through telenephrology services and then admitted subsequently. For patients with mild symptoms, daily assessment was performed to guide the need for admission and immunosuppression modification. Laboratory markers of inflammation and coagulation such as serum ferritin, interleukin-6, C-reactive protein (CRP), lactate dehydrogenase, and D-dimers were sent at admission for all patients. In home-isolated patients, laboratory parameters were noted from available clinical records. After admission, serum procalcitonin was tested on suspicion of superadded sepsis, such as new-onset fever, unexplained tachycardia, neutrophilic leukocytosis, and new infiltrates on chest radiographs, in addition to appropriate cultures.

Statistical analyses

Statistical analyses were done using the SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). While continuous data were presented as medians with interquartile range and compared using Mann–Whitney test, categorical variables were presented as frequency or percentages and compared using the Chi-square test or Fisher's exact test, as appropriate. A P < 0.05 was considered to be statistically significant.

Declaration of patient consent

The authors certify that anonymized datasets were used for the purpose of the study and no patient identification markers were utilized. The same was approved by the ethics committee.

Ethics statement

The study was approved by the Institutional Ethical Committee (IEC 89/21). The guidelines as per the Declaration of Helsinki were followed.


  Results Top


Epidemiology

[Table 1] describes the baseline characteristics, transplant-related, and COVID-related clinical and laboratory features of patients who presented with COVID illness in the first and second waves. The KTRs who presented during the second wave were not significantly different than those presenting during the first wave, in terms of sex, place of residence, related versus unrelated donors, time since transplant, induction agent used, number of prior rejection episodes, presenting symptoms such as fever, cough, breathlessness, and diarrhea, and median duration of fever before the diagnosis of COVID illness. Although COVID-19 vaccination had commenced before the second wave, only two KTRs had been vaccinated, both while they were in the transplant waitlist (the existing national guidelines at the time supported vaccination for those above 45 years of age with end-stage renal disease as a comorbidity). Both these vaccinated KTRs were in home isolation with mild COVID illness.
Table 1: Comparison of baseline clinical and laboratory characteristics of kidney transplant recipients (survivors and nonsurvivors) in the first and second waves of the COVID pandemic

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Severity of COVID illness and graft dysfunction

[Table 2] compares COVID management during the first and second waves, as well as aspects related to immunosuppressive medications. Presentation with severe COVID illness was significantly higher in the second wave than in the first wave. This explains the significantly higher rise in inflammatory markers and D-dimer values in the second wave. This was also reflected in the higher use of oxygen by nonrebreathing masks and noninvasive and invasive mechanical ventilation during the second wave. Similarly, the occurrence of acute graft dysfunction and the need for renal replacement therapy increased during the second wave. Only mild graft dysfunction was detected in 3/18 KTRs during the second wave, although renal replacement therapies were utilized in five patients. Only one patient had a serum creatinine >4 mg/dl, and she was diagnosed with allograft pyelonephritis and mucormycosis postmortem. These patients underwent sustained low-efficiency hemodialysis[3] and continuous renal replacement therapies[2] for fluid and acid–base management in the intensive care unit (ICU).
Table 2: Comparison of management strategies of immunosuppressive modification and COVID illness in kidney transplant recipients (survivors and nonsurvivors) in the first and second waves of the COVID pandemic

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Management of COVID illness and immunosuppressive medications

In terms of management, only patients with moderate and severe COVID illness were hospitalized in the second wave, whereas 4/5 patients hospitalized during the first wave, had only mild COVID illness (as per the existing COVID protocols). In accordance with the greater severity of COVID illness in the second wave, reduction and stoppage of antiproliferative, hiking up of steroids, and the usage of heparin were predictably higher during the second wave. Remdesivir use was significantly lower in the second than in the first wave. Tocilizumab and convalescent plasma were not used in any of the patients.

Secondary infections

Serum procalcitonin values were available for only one patient during the first wave, a KTR who died in the 2nd week of acute pancreatitis, who was found to have contracted COVID infection during his stay in the ICU and died without developing any pulmonary involvement. Among the KTRs admitted during the second wave, serum procalcitonin values were available for 8/18 patients, with a median value of 54.5 pg/ml (ranging between 0.5 and >200 pg/ml) and in samples drawn at a median duration of 13 days (ranging between 8 and 22 days) from admission. Two cases of mucormycosis, one with rhinocerebral and the second one with allograft involvement were also noted who succumbed during the second wave.


  Discussion Top


The COVID-19 pandemic adversely affected annual rates of solid organ transplantation, including renal transplants. Early on, an advisory by the Indian Government (MOHFW) suspended elective living donor and nonurgent deceased donor kidney transplants during the COVID-19 pandemic leading to restricted transplant activities during the national lockdown.[7]

A few studies have provided insight into the epidemiology and management of the second wave of the COVID pandemic in KTRs from different regional transplant centers, and the variation in outcomes such as mortality might reflect differences in prevalent strains, vaccination status, and health-care delivery.[8],[9],[10],[11],[12] The reasons for the high mortality in ours, as well as, some other cohorts from different parts of the world are unknown.[13] However, as only patients with moderate and severe COVID illness were admitted to our center during the second wave, it is possible that certain “high-risk” patients may have been missed early in the course, and therefore, might have been deemed to have a severe illness at admission. It is well-known that the outcome depends on the severity of disease at the time of presentation. All eight patients who were hospitalized during the second wave required direct ICU admission. Other studies also reported high mortality rates among patients admitted to the ICU, and in mechanically ventilated patients. A large multicenter cohort study by Kute et al. had an overall mortality of 11.6%, which increased to 47% for patients in the ICU and 96.7% for patients on mechanical ventilation.[5] Furthermore, high rates of secondary bacterial infections (in addition to two-documented cases of fatal mucormycosis) might have contributed to the increase in mortality in our cohort. KTRs with COVID-19 illness also carry a greater risk of developing acute kidney injury, which correlated with the severity and requirement of ICU admission in the present study. However, the majority of patients had only mild graft dysfunction, as in previous studies.[5],[14],[15]

Hitherto, KTRs have been excluded from major therapeutic trials of COVID management, and the use of drugs such as remdesivir and tocilizumab in KTRs comes from other case series, with no clear evidence of their safety and efficacy in this population.[3],[4],[5] As the patients were already on steroid-based triple immunosuppression with doses of prednisolone ranging from 5 to 10 mg/day, steroids were increased up to 30–40 mg/day of prednisolone for 10 days, in accordance with available studies and guidance.[16] Conversion from prednisolone to dexamethasone was done if the patient required high-flow oxygen or mechanical ventilation. Remdesivir was administered to all hospitalized transplant patients per institutional protocol in the first wave, whereas in the second wave, only eight were hospitalized, and six of the eight received remdesivir (the remaining two had transaminitis at presentation, and were therefore not prescribed). No dose modification was performed for patients with renal dysfunction, as per existing evidence. The overall lower use of remdesivir in the second wave was due to lower proportion of hospitalization. Among all patients who received remdesivir, none had to discontinue the drug due to transaminitis. In view of a high propensity for secondary infections, tocilizumab could not be used in our patients. All the patients with moderate and severe COVID illness received heparin, and none reported excessive bleeding or thrombocytopenia requiring drug cessation. The evidence available at the onset of the second wave did not support the use of convalescent plasma, therefore, none of the KTRs received this therapy during the second wave.[6]

The reasons for the high morbidity and mortality for KTRs during the second wave of the COVID pandemic could be multifactorial. the mortality in the general population was also higher than in the first wave, the greater virulence of the B.1.617 variant of the SARS-CoV-2 virus, and the greater strain on health-care resources and delivery during the peak of the second wave.[14],[15] The use of telenephrology services and outpatient laboratory services for inflammatory markers (serum ferritin, lactate dehydrogenase, CRP, etc.) proved useful for KTRs with mild illness being managed on home isolation, but probably failed in identifying “high-risk” patients who ultimately died.

Limitations

The study is limited by its retrospective design, lack of follow-up inflammatory markers and cardiac function markers, and also that further studies were not undertaken to confirm the variants of SARS-CoV-2 were isolated from samples taken from KTRs to analyze causes for the greater severity of illness observed in KTRs during the second wave.


  Conclusions Top


A greater number of KTRs presented with moderate and severe COVID illness, with respiratory symptoms and required ICU admissions during the second wave of the COVID pandemic in this region situated in northern India. Mild graft dysfunction and secondary infections correlated with the severity of COVID illness. Mortality was strongly associated with the severity of the illness. Time since transplant and maintenance immunosuppression did not affect the severity of illness at presentation, during both waves of the COVID pandemic. In view of the heightened morbidity and mortality in this subset, and poorer vaccine responses in the posttransplant period, COVID vaccination before kidney transplantation should be prioritized by policymakers and future guidelines.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kute V, Ramesh V, Shroff S, Guleria S, Prakash J. Deceased-Donor organ transplantation in India: Current status, challenges, and solutions. Exp Clin Transplant 2020;18:31-42.  Back to cited text no. 1
    
2.
Samarasekera U. India grapples with second wave of COVID-19. Lancet Microbe 2021;2:e238.  Back to cited text no. 2
    
3.
Angelico R, Blasi F, Manzia TM, Toti L, Tisone G, Cacciola R. The management of immunosuppression in kidney transplant recipients with COVID-19 disease: An update and systematic review of the literature. Medicina (Kaunas) 2021;57:435.  Back to cited text no. 3
    
4.
Mahalingasivam V, Craik A, Tomlinson LA, Ge L, Hou L, Wang Q, et al. A systematic review of COVID-19 and kidney transplantation. Kidney Int Rep 2021;6:24-45.  Back to cited text no. 4
    
5.
Kute VB, Bhalla AK, Guleria S, Ray DS, Bahadur MM, Shingare A, et al. Clinical profile and outcome of COVID-19 in 250 kidney transplant recipients: A multicenter cohort study from India. Transplantation 2021;105:851-60.  Back to cited text no. 5
    
6.
Government of India MoHFW, Directorate General of Health Services. Revised Guidelines on Clinical Management of COVID-19; 2020. Available from: https://www.mohfw.gov.in/pdf/RevisedNational Clinical Management Guideline for COVID1931032020.pdf. [Last accessed on 2021 Oct 09].  Back to cited text no. 6
    
7.
Martino F, Plebani M, Ronco C. Kidney transplant programmes during the COVID-19 pandemic. Lancet Respir Med 2020;8:e39.  Back to cited text no. 7
    
8.
Elec FI, Bolboacă SD, Muntean A, Elec AD, Cismaru C, Lupşe M, et al. Comparing the first and second wave of COVID-19 in kidney transplant recipients: An East-European perspective. Eur Surg Res 2022;63:25-32.  Back to cited text no. 8
    
9.
Kute VB, Meshram HS, Navadiya VV, Chauhan S, Patel DD, Desai SN, et al. Consequences of the first and second COVID-19 wave on kidney transplant recipients at a large Indian transplant centre. Nephrology (Carlton) 2022;27:195-207.1  Back to cited text no. 9
    
10.
Tatapudi RR, Kopparti VR, Poosapati A, Metta S, Gongada AR, Vedulla B. SARS-CoV-2 infection in kidney transplant recipients: A single-centre study of 20 cases from India. Int J Nephrol 2021;2021:2243095. doi: https://doi.org/10.1155/2021/2243095.  Back to cited text no. 10
    
11.
Arumugam V, Sastry BV, Solomon DJ, Gopalakrishnan N, Kannan BS, Shankar P, et al. Clinical characteristics and outcome of novel coronavirus disease in kidney transplant recipients: A single-centre prospective observational study. Ind J Transplant 2021;15:189-98.  Back to cited text no. 11
    
12.
Bhandari G, Tiwari V, Gupta A, Bhargava V, Malik M, Gupta A, et al. COVID-19 infection in renal transplant patients: Early report from India. Indian J Nephrol 2021;31:271-5.  Back to cited text no. 12
  [Full text]  
13.
Caillard S, Anglicheau D, Matignon M, Durrbach A, Greze C, Frimat L, et al. An initial report from the French SOT COVID Registry suggests high mortality due to COVID-19 in recipients of kidney transplants. Kidney Int 2020;98:1549-58.  Back to cited text no. 13
    
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Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M. COVID-19 infection in kidney transplant recipients. Kidney Int 2020;97:1076-82.  Back to cited text no. 14
    
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Elias M, Pievani D, Randoux C, Louis K, Denis B, Delion A, et al. COVID-19 infection in kidney transplant recipients: Disease incidence and clinical outcomes. J Am Soc Nephrol 2020;31:2413-23.  Back to cited text no. 15
    
16.
Maggiore U, Abramowicz D, Crespo M, Mariat C, Mjoen G, Peruzzi L, 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;35:899-904.  Back to cited text no. 16
    



 
 
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