Kidney Res Clin Pract > Volume 40(3); 2021 > Article
Meshram, Kute, and Chauhan: BK polyomavirus infection following COVID-19 infection in renal transplant recipients: a single-center experience
Coronavirus disease 2019 (COVID-19) has affected the transplantation community worldwide. Reports of transplant patients acquiring COVID-19 infections are extensive with diverse mortality rates [1]. Follow-up studies of COVID-19 in transplant communities are lacking. There are limited data on the association of the BK polyomavirus (BKPyV) with active COVID-19 infection in kidney transplant recipients (KTRs) [2,3]. Currently, theoretical concerns exist related to graft dysfunction or loss during the post-COVID-19 follow-up period in KTRs. This study aimed to explore the clinical profile, outcomes, and follow-up experiences of KTR patients who developed BKPyV after COVID‐19. This was a single-center retrospective analysis of a study approved by our Institutional Ethical Board (ECR/143/Inst/GJ/2013/RR-19 with application No: EC/App/20Jan21/08) and was conducted in compliance with the Declaration of Helsinki. KTR patients admitted for COVID-19 infection during the study period from June 2020 to December 2020 who developed BKPyV after a positive COVID-19 diagnosis were included. We conducted extended and close monitoring and follow-up of the cohort in the physical, clinical, and psychological domains. Follow-up BKPyV testing was conducted at 1-month after discharge, followed by every 3 months thereafter. Testing also was performed in cases of increasing creatinine.
We identified 11 cases of BKPyV after infection in 167 total COVID-19 KTR cases. Table 1 shows the overall summary of the study. The median age of the cohort was 45 years (range, 29-56 years), with male predominance (90.9%). The majority of the cohort had comorbidities (72.7%), underwent live-related-donor transplantation (72.7%), and received thymoglobulin (81.8%) upon admission for COVID-19. The baseline median serum creatinine was 1.44 mg/dL (range, 1.3-1.9 mg/dL). COVID-19 severity was categorized as mild (9%), moderate (45%), and severe cases (46%) [4]. Acute kidney injury was reported in all cases, and acute respiratory distress syndrome developed in 18.2% of KTR patients, with one fatality during COVID-19 admission. Five cases (45.5%) received steroids during acute COVID-19 infection. At baseline, no cases showed BKPyV in the blood. Baseline polymerase chain reaction (PCR) urine testing of the cohort did not detect BKPyV in most cases (81.8%). Table 2 shows the laboratory parameters of the cohort. The median BKPyV blood and urine PCR results during acute COVID-19 infection were 2,509 copies/mL (range, 280-41,746 copies/mL) and 4,433,366 copies/mL (range, 7,602-198,681,183 copies/mL), respectively.
The follow-up period after BKPyV diagnosis was 7 months (range, 5-8 months). BKPyV was detected in the blood during the follow-up period in only one patient. The BKPyV PCR urine values of the cohort were less than those detected in 63.6% of the follow-up cases. No graft loss or graft dysfunction was reported in the cohort. No patient developed sensitization, urine microhematuria, or proteinuria during the follow-up period. Radiological resolution [5] of COVID-19 infection was defined as the absence of any chest radiographic abnormality potentially related to the infection; this type of resolution was seen in 91.6% of KTR cases and resolved after a median of 3 months of follow-up. No multisystemic sequelae were reported. One case was readmitted 1 week after discharge and died due to secondary fungal infection (aspergillosis) after 1 month.
Our report could simply indicate that the natural history and course of BKPyV happened to coincide with COVID-19 infection, and there might be no actual association between the two; however, reactivation of viruses like BKPyV is a high-risk factor for graft loss in transplant patients [6]. BKPyV causes complex changes in immunity and weakens the immune response, which could potentially aggravate the immune/graft injury often present in COVID-19 infection [7]. Elevated levels of inflammatory cytokines in COVID-19 infection can lead to greater transcription of the BKPyV genome [8]. The use of thymoglobulin as an induction agent could have been a confounding factor for BKPyV, but the institutional protocol of using a low dosage of thymoglobulin (1.5 mg/kg) hinders this connection. Moreover, at our center, the incidence of BKPyV in COVID-19 patients was 6.6% (11 of 167 patients), which was higher than the rate reported in normal follow-up or in non-COVID-19 admissions (1.3%). While we were unable to show a definite association of BKPyV with COVID-19 infection, the use of steroids to treat these patients and COVID-19 infection itself are both risk factors for an increase in number of BKPyV in KTRs. Therefore, we suggest screening for BKPyV in COVID-19 patients.
One limitation of this study was its small sample size. To date, this is the largest cohort of KTRs with BKPyV after COVID-19 infection.
In summary, we report BKPyV following COVID-19 with no graft loss during the follow-up period. We suggest screening for BKPyV in all renal transplant patients with active COVID-19 infection (especially in patients with a history of BKPyV and in severe COVID-19 infection) as a safe option to avoid complications.

Notes

Conflicts of interest

All authors have no conflicts of interest to declare.

Authors’ contributions

Conceptualization, Data curation, Formal analysis, Investigation: All authors

Writing-original draft: All authors

Writing-review & editing: All authors

All authors read and approved the final manuscript.

Table 1.
Characteristics of the cohort with BKPyV following SARS-CoV2 infection
Characteristic Case No.
1 2 3 4 5 6 7 8 9 10 11
Age (yr) 57 23 55 41 28 35 29 45 47 56 69
Sex Male Male Male Male Male Male Male Male Male Female Male
Body mass indexa > 30 kg/m2 Yes No Yes No No Yes No Yes Yes Yes Yes
Blood group B+ B+ A+ O+ O+ B+ B+ B+ AB+ A+ B+
Comorbidity DM, obesity No DM, HTN, obesity HTN No HTN, obesity No HTN, obesity HTN, obesity HTN, CMV, TB, obesity DM, HTN, obesity
Cause of end-stage renal disease DM Unknown DM Unknown CGN HTN Unknown Obstructive Unknown HTN DM
Time from transplantation to COVID-19 detection (mo) 12 4 26 64 5 66 26 27 3 15 25
Transplant type Living related Living related Living related Living related Deceased donor Living related Living related Deceased donor Living Living Deceased
related related donor
Induction agents ATG ATG ATG ATG IL-2 ATG ATG IL-2 ATG ATG ATG
Maintenance immunosuppression S + Tac + MMF S + Tac + MMF S + Tac + MMF S + Tac S + Tac + MMF S + Tac + AZA S + Tac + MMF S + Tac + MMF S + Tac + MMF S + Tac S + Tac + MMF
Tac level (ng/mL) 8 7.2 6 5.2 8 4.2 NA 8 9.2 7.4 6.2
Baseline serum creatinine (mg/dL) 1.4 1.3 0.9 1.3 1.4 1.5 2.5 2 1.6 1.4 2.2
AKI during admission 1 1 1 1 1 2 1 1 HD 1 3
Follow-up creatinine (mg/dL) 1.4 1.2 1.1 1.3 1.4 1.5 2.2 2 3.1 1.6 HD
History of antirejection therapy No No No No No No No No No No No
Presenting complaint Fever Fever, cough, dyspnea Fever, cough, dyspnea, diarrhea Cough, Cough Dyspnea Cough, dyspnea Fever, cough Fever, cough, dyspnea, diarrhea Fever, cough, dyspnea Fever, cough, dyspnea
dyspnea
COVID-19 severity Mild Moderate Severe Moderate Moderate Severe Moderate Moderate Severe Severe Severe
Radiological abnormalities at admission No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Duration of hospital stay (day) 5 7 9 9 8 11 6 7 14 10 12
Anti COVID-19 therapy Azithromycin O Steroids, remdesivir O R Steroids, remdesivir O R Steroids, remdesivir, plasma therapy Steroids, remdesivir, plasma therapy, Steroids, remdesivir
Tocilizumab
Change in immunosuppression MMF/CNI MMF/CNI MMF/CNI CNI MMF/CNI AZA/CNI MMF/CNI MMF/CNI MMF/CNI CNI MMF/CNI
Follow-up after BKPyV diagnosis (mo) 10 9 8 8 7 7 6 5 2 5 1
BKPyV quantitative (copies/mL)
 Baseline
  Blood ND ND ND ND ND ND ND ND ND ND ND
  Urine 63,795,828 ND ND ND ND 2254 ND ND ND ND ND
 Acute COVID-19
  Blood 41,746 30,686,658 77 294 1,878 280 7,800 89 2,509 240,900 20,364
  Urine 1,898,962,063 100,846,288,896 4,433,366 3,313 - 7,602 323,136 198,681,183 2,460,617 35,608,162 150,220,635
 Follow-up COVID-19
  Blood 104 ND ND ND ND ND ND ND ND ND NA
  Urine 331,931 2,077 ND ND ND ND ND 249,519,444 15,971 ND
Immunosuppression modification for BKPyV MMF stopped MMF stopped MMF tapered CNI tapered MMF stopped AZA stopped MMF stopped MMF tapered MMF stopped MMF stopped MMF/CNI stopped
Outcome and follow-up Uneventful Uneventful Uneventful Uneventful Uneventful Uneventful Uneventful Uneventful Died 1 mo postdischarge Uneventful Died at day 14

AKI, acute kidney injury; ATG, thymoglobulin; AZA, azathioprine; BKPyV, BK polyomavirus; CGN, chronic glomerulonephritis; CMV, cytomegalovirus; CNI, calcineurin inhibitors; COVID-19, coronavirus disease 2019; DM, diabetes mellitus; F, female; HD, hemodialysis; HTN, hypertension; IL-2, interleukin 2 blocker; M, male; MMF, mycophenolate mofetil; NA, not available; ND, not detected; O, other supportive therapy; R, remdesivir; S, steroid; SARS-CoV2, severe acute respiratory syndrome coronavirus 2; Tac, tacrolimus; TB, tuberculosis.

a Body mass index value > 30 kg/m2 was defined as obesity.

Table 2.
Laboratory and inflammatory markers in the cohort at admission due to COVID-19 infection
Laboratory parameter (normal range) Case No.
1 2 3 4 5 6 7 8 9 10 11
Hemoglobin (13-16 g/dL) 10.6 12.5 13.1 11.4 14.8 14.4 17.1 9.3 17.1 8.5 7.8
Total leukocyte count (4-11 × 103cells/L) 3,280 4,990 2,660 5,370 5,040 12,400 6,800 4,850 11,830 4,000 13,600
Polymorphs (60%-70%) 71 75 55 72 62 78 90 74 8 69 83
Lymphocyte (25%33%) 26 23 42 25 35 19 8 23 16 27 15
Platelet counts (150-400 × 109cells/L) 441 190 272 178 244 261 124 282 285 178 279
D-dimer (200-500 ng/mL) 3,360 630 9,870 NA 360 2,450 290 1,110 2,330 NA 2,880
Procalcitonin (<0.5 ng/mL) 0.05 0.05 0.05 NA 0.05 0.27 0.06 0.31 11.6 7.9 NA
Highly sensitive C protein (0-10 mg/L) 29 30.9 4.8 6.1 21.8 51.4 42.1 74.2 210 NA 189
Aspartate transferase (0-40 IU/L) 59 42 30 18 24 32 19 25 18 40 11
Interleukin 6 (<7 pg/mL) 8.2 58.3 NA 1,531 NA NA 25.7 14.5 24.1 NA 470
Lactate dehydrogenase (100-190 IU/L) 387 510 272 322 391 523 550 292 NA NA 534
Ferritin (13-400 ng/mL) 69.0 998.0 232.0 178.0 64.0 477.0 120.0 311.0 373.0 NA 465.0
Serum albumin (3.2-5.0 g/dL) 3.7 2.8 3.0 3.1 2.9 2.9 3.4 2.8 3.0 3.1 3.1
Blood urea nitrogen (13-45 mg/dL) 44 45 33 41 54 33 48 59 81 22 69

COVID-19, coronavirus disease 2019; NA, not available.

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ORCID iDs

Hari Shankar Meshram
https://orcid.org/0000-0001-9148-8168

Vivek B. Kute
https://orcid.org/0000-0002-0002-2854

Sanshriti Chauhan
https://orcid.org/0000-0001-7385-5614

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