Received: 8 July 2020

Revised: 21 July 2020

Accepted: 22 July 2020

DOI: 10.1111/1744-9987.13566

LETTER TO THE EDITOR

Prolonged shedding of SARS-CoV-2 in COVID-19 infected
hemodialysis patients
Dear Editor,
An outbreak of coronavirus disease 2019 (COVID-19),
now known to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that began in China
in December 2019, has since spread rapidly throughout
the world.1 There are several reports of hemodialysis
patients with COVID-19.2–4 Hemodialysis patients appear
to be a population at high risk for severe COVID-19,
because factors identified as risk factors for severe
COVID-19 are often present in these patients: old age,
hypertension, cardiovascular comorbidity, and diabetes
mellitus. In addition, these patients also show impaired
antiviral immune responses, because of the impaired kidney function. On the other hand, hemodialysis patients
may not be at a higher risk for more severe COVID-19 inother respects: They are also aware of their vulnerable
condition, they know that they should seek medical
advice immediately when they have fever or other complaints, and they have an immunosuppressed state which
may attenuate the hyperinflammatory response observedin the stage of severe COVID-19. The usual clinicalcourse of hemodialysis patients with COVID-19 is not yetclear. We examined 5 hemodialysis patients with
COVID-19 at our hospital and report, herein, the prolonged persistence of a positive result of the PCR test for
SARS-CoV2 in hemodialysis patients.

1 | P A T I E N T S A N D ME T H O D SFive hemodialysis patients transferred to our hospital
after treatment of the acute phase of COVID-19 wereenrolled in this study. Clinical data were collected fromthe patients' records. The duration of positive results of
the real-time reverse transcriptase-polymerase chain
reaction (RT-PCR) test for SARS-CoV-2 was investigatedin these patients. The PCR tests were performed on nasopharyngeal swabs. The data are expressed as themeans ± SD. This study was conducted in accordancewith the principles of the Declaration of Helsinki andwith the approval of the research ethics committee ofSangenjaya Hospital (Approved No. R0206).

2 | RESULTS
The characteristics of the five patients enrolled in thisstudy are shown in Table 1. The mean age was
74 ± 9 years. Diabetic nephropathy was the cause of theend-stage kidney disease in the majority (60%). The mean
dialysis vintage was 9.4 ± 10.2 years. All five patients had
a definite history of contact with an infected person. Allfive received treatment with favipiravir. Two patients also
received tocilizumab, ivermectin or a steroid in addition.
Ciclesonide was used in one patient. The fever and othersubjective symptoms resolved soon after the start of treatment in all the five patients. However, the results of thePCR test for SARS-CoV-2 remained positive for 24–37(mean, 29 ± 6) days. The first negative PCR test result
was confirmed between 27 and 42 (mean, 34 ± 7) days
after the onset of symptoms (Figure 1).

3 | DISCUSSION
We report here that in hemodialysis patients with
COVID-19, it takes a long time before the PCR test turns
negative. The mean length of time over which the PCR
test for SARS-CoV-2 remained positive in our patientswas 24–37 (mean, 29 ± 6) days. Prolonged shedding ofSARS-CoV-2 in COVID-19 infected hemodialysis patientswas observed.
In most general patients with symptomatic COVID-19
infection, viral RNA in the nasopharyngeal swab
becomes detectable as early as on day 1 of symptom onset
and peaks within the first week of symptom onset, andthe positivity rate of the test starts to decline by week
3, with the test result becoming negative soon thereafterin most patients.5 In our study, the PCR test result
remained positive for more than 24 days after the onsetof disease in all the five hemodialysis patients. Therefore,
we report that hemodialysis patients may show prolonged persistence of positive results of the PCR test forSARS-CoV-2.
One of the reasons for the prolonged persistence of apositive test result may be the tendency of hemodialysis© 2020 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy
Ther Apher Dial. 2020;1–3.

wileyonlinelibrary.com/journal/tap

1

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LETTER TO THE EDITORTABLE 1

The characteristics of the 5 hemodialysis patientswith COVID-19Characteristics

QuantityAge

74 ± 9Gender (M/F)

3/2

Cause of ESKD
Diabetic nephropathy

3

Chronic glomerulonephritis

1Unknown

1Dialysis vintage (years)

9.4 ± 10.2

Treatment
Favipiravir

5Tocilizumab

2

Ivermectin

2

Steroid

2Ciclesonide

1

Length of time over which the PCR test for SARSCoV-2 remained positive (days)

29 ± 6

Note: Mean ± SD.
Abbreviation: ESKD, end stage kidney disease.

F I G U R E 1 Days since onset and nasopharyngeal swabs PCR
positive rate. The results of the PCR test for SARS-CoV-2 remained
positive for 24 to 37 (mean, 29 ± 6) days. The first negative PCR
test result was confirmed between 27–42 (mean, 34 ± 7) days after
the onset of symptoms

patients with COVID-19 to follow a severe clinical course.
They frequently have several risk factors for severe
COVID-19. The mortality rate of COVID-19 in Japanese
population was 4.1% (985/24132),6 while that of Japanesehemodialysis patients was 17.6% (22/125).7 In severely illhospitalized patients with COVID-19, a positive test
result of PCR may persist beyond 3 weeks after the onsetof illness, whereas the test turns negative by this time inmost cases with mild disease.5 In hemodialysis patientswith COVID-19, it might be better to remain isolated longer than ordinary infected patients to prevent the environmental contamination in hemodialysis units.
In addition, hemodialysis patients also show impaired
antiviral immune responses which could also explain theprolonged persistence of a positive PCR test result.
A “positive” PCR test result only reflects the presence ofviral RNA, and does not necessarily indicate the presenceof viable virus. In some cases, viral RNA has been
detected by PCR even beyond week 6 after the first positive test. In a few cases, a positive test result has evenbeen reported after 2 consecutive negative results of PCR
performed at least 24 hours apart. It remains unclear if
the finding in these cases reflects a testing error, reinfection, or reactivation. In a study of nine patients, attempts
to isolate the virus in culture were not successful beyond
day 8 after the onset of illness, which correlates with thereported decline of infectivity of the patients after the firstweek of the disease.6 That may be the reason, at least inpart, for the changes announced by the Japanese Ministryof Health, Labour and Welfare to the conditions necessary for discharge from the hospital of patients with
COVID-19. While the Ministry had once recommended
at least two consecutive negative results of the PCR test
before patients with COVID-19 could be discharged fromthe hospital, after reconsidering the evidence, it now recommends that patients may be discharged without a PCR
test if they have remained symptom-free for 72 hours andat least 10 days have elapsed after the onset of symptoms.
The significance of the prolonged persistence of positive
PCR test results in hemodialysis patients remains
unclear. The patients in our study showed resolution of
their symptoms and signs soon after the start of treatment and the persistently positive test results may justreflect the trapped RNA of a non-infectious virus in thesepatients too, as in the general population.
One of the important limitations of our study was that
we did not know the detailed clinical courses of thepatients from the disease onset, as they were transferredto our hospital after treatment of the acute phase. And,
we also did not know the characteristics of main hemodialysis population which these patients came from. Accumulation of further cases is necessary.

4 | CONCLUSION
Prolonged shedding of SARS-CoV-2 in COVID-19
infected hemodialysis patients was observed. It may bebetter to isolate hemodialysis patients with COVID-19
longer than ordinary infected patients to prevent environmental contamination in hemodialysis units.

LETTER TO THE EDITOR

3CONFLICT OF INTEREST
The authors declare that no potential conflict of interest.
Shigeru Otsubo1,2
Yumi Aoyama1,3
Kayoko Kinoshita1
Taijiro Goto1
Yuriko Otsubo1
Daisuke Kamano4
Rena Sumura4
Satoki Shinzawa4
Tatsuki Abe4
Ryunosuke Noda4
Ryu Kobayashi4
Mai Yanagi4
Kosaku Nitta3
Yoshitaka Ishibashi41

Department of Nephrology, Sangenjaya Hospital, Tokyo,Japan2
Department of Blood Purification, Tohto Sangenjaya
Clinic, Tokyo, Japan3
Department of Nephrology, Tokyo Women's Medical
University, Tokyo, Japan
4
Division of Nephrology, Japanese Red Cross Medical
Center, Tokyo, Japan
Correspondence
Shigeru Otsubo, MD, PhD, FJSIM, Department ofNephrology Sangenjaya Hospital, Sangenjaya Hospital,

1-21-5 Sangenjaya, Setagaya-ku, Tokyo 154-0024, Japan.
Email: sotsubo33@gmail.com
ORCID
Shigeru Otsubo

https://orcid.org/0000-0002-5496-0790

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html
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