Volume 26, Number 11—November 2020
Research Letter
Detection of SARS-CoV-2 in Hemodialysis Effluent of Patient with COVID-19 Pneumonia, Japan
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Ayako Okuhama, Masahiro Ishikane
, Daisuke Katagiri, Kohei Kanda, Takato Nakamoto, Noriko Kinoshita, Naoto Nunose, Takashi Fukaya, Isao Kondo, Harutaka Katano, Tadaki Suzuki, Norio Ohmagari, and Fumihiko Hinoshita
, Daisuke Katagiri, Kohei Kanda, Takato Nakamoto, Noriko Kinoshita, Naoto Nunose, Takashi Fukaya, Isao Kondo, Harutaka Katano, Tadaki Suzuki, Norio Ohmagari, and Fumihiko HinoshitaAbstract
We report detection of severe acute respiratory syndrome coronavirus 2 RNA in hemodialysis effluent from a patient in Japan with coronavirus disease and prolonged inflammation. Healthcare workers should observe strict standard and contact precautions and use appropriate personal protective equipment when handling hemodialysis circuitry from patients with diagnosed coronavirus disease.
Since December 2019, coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major health threat worldwide (1). Reports have been published on COVID-19 among patients receiving hemodialysis (2), but none have evaluated whether HD effluent is infectious. In addition, handling of hemodialysis circuitry is not mentioned in US Centers for Disease Control and Prevention (CDC) guidelines for COVID-19 infection control and prevention in dialysis facilities (3). We report detection of SARS-CoV-2 RNA in hemodialysis effluent from a patient with COVID-19 pneumonia and prolonged inflammation.
Figure. Chest computed tomography (CT) scan of a patient on hemodialysis diagnosed with positive reverse transcription PCR for severe acute respiratory syndrome coronavirus 2 in hemodialysis effluent, Japan. A) Chest CT at...
The patient, a 79-year-old man with end-stage renal disease (ESRD) due to IgA nephritis, had been receiving maintenance hemodialysis 3 times per week for 12 years. Six days before admission, he started having a fever and cough. Four days later, he had a nasal swab test for SARS-CoV-2 RNA. Quantitative reverse transcription PCR (qRT-PCR) (4) of the patient’s specimen was positive, and he was admitted to the hospital. At admission, his body temperature was 37.7°C and oxygen saturation was 98% on room air. Multiple bilateral patchy ground glass opacities (GGO) were observed on the patient’s chest computed tomography (CT) scan (Figure, panel A). Blood test results showed C-reactive protein (CRP) of 8.8 mg/dL and leukocyte count of 4,470 cells/μL. Although we started him on hydroxychloroquine 200 mg and azithromycin 500 mg, each 2 times/day, he had a fever (>38.0°C) on day 2 of his hospitalization. A follow-up chest CT on hospitalization day 5 showed worsening COVID-19 pneumonia and expanding GGO areas (Figure, panel B).
During the patient’s hospitalization, we administered hemodialysis by using a polysulfone membrane dialyzer in a private depressurized room with dedicated machines. We tested hemodialysis effluent for SARS-CoV-2 on day 2. PCR results showed SARS-CoV-2 RNA of 157.9 copies/μL with cycle threshold (Ct) values of 38.3 at 1 hour after starting hemodialysis but were negative on effluent collected at 2 hours. Because the patient’s fever persisted and CRP levels remained high, on hospitalization days 9, 11, and 15 we performed direct hemoperfusion by using a β2 microglobulin adsorbent column (Lixelle-DHP) to absorb cytokine. On hospitalization day 10, the patient became afebrile and CRP began decreasing until it reached 5.9 mg/dL on hospitalization day 15. On hospitalization day 16, chest CT showed markedly improved pneumonia (Figure, panel C), and the patient was discharged (Table).
Our case highlights 3 things. First, inflammation and clinical symptoms of COVID-19 can persist in patients on hemodialysis. COVID-19 is thought to progress in a 2-stage manner: viral replication and hyperinflammation (1). Hyperinflammation starts 7–10 days after symptom onset and involves extensive lung areas. This patient’s fever persisted for >13 days, with pneumonia and CRP worse at 11 days after fever onset. Hyperinflammation appeared to progress slower and be maintained longer than in patients who are not receiving hemodialysis, which might be related to immune system dysfunction in patients with ESRD (5). Second, although SARS-CoV-2 RNA has been detected in various clinical specimens (6,7), our case demonstrates it also can be detected in hemodialysis effluent, even though we did not detect SARS-CoV-2 RNA in blood, as noted in a previous case (6). We hypothesized that only a small amount of fragmented RNA might pass through the dialysis membrane at the start of hemodialysis, but no marked fragments remain in the blood as a session progresses. Third, our case suggests Lixelle-DHP can have therapeutic effects for patients on hemodialysis. Although we did not measure the patient’s predialysis and postdialysis cytokine levels, use of a blood purification technique might alleviate the effects of cytokine in COVID-19 pathophysiology due to its proven effect in reducing plasma cytokine levels in general (8).
Our report has several limitations. First, we did not confirm the duplicability of PCR results of hemodialysis effluent. We performed PCR only once and did not reevaluate the same specimen, even though the Ct was high. Second, the infectiousness of hemodialysis effluent is unclear. Its viability should be quantified by endpoint titration on authorized cell lines, as previously reported (9). Third, this is a single case report. Despite these limitations, we cannot underestimate the infectiousness of hemodialysis effluent. We performed dialysis in a private room with dedicated machines. We also conducted strict standard and contact precautions when handling HD circuitry, following CDC recommendations for preventing transmission of hepatitis B virus infection among patients on HD (10).
In conclusion, we report positive qRT-PCR results for SARS-CoV-2 RNA from hemodialysis effluent in a patient receiving renal dialysis. The clinical course of our patient was characteristic of the persistent inflammation of COVID-19 and shows the potential effectiveness of Lixelle-DHP as a treatment in patients on hemodialysis. Our case indicates that strict standard and contact precautions are essential when handling hemodialysis circuitry of patients with COVID-19. As more patients on hemodialysis contract SARS-CoV-2, we expect further studies on infection control and prevention in dialysis facilities and on the effectiveness of Lixelle-DHP in treating patients with COVID-19.
Dr. Okuhama is a clinical senior resident at the Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan. Her research interests include emerging infectious diseases and public health.
Acknowledgment
We thank all the clinical staff at our hospital for their dedication to patient care and the patient, who provided written informed consent to have his clinical details presented in this report.
References
- Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
- Wang R, Liao C, He H, Hu C, Wei Z, Hong Z, et al. COVID-19 in hemodialysis patients: A report of 5 cases. Am J Kidney Dis. 2020;76:141–3.
- US Centers for Disease Control and Prevention. Interim guidance for infection prevention and control recommendations for patients with suspected or confirmed COVID-19 in outpatient hemodialysis facilities 2020 Apr 21 [cited 2020 Apr 22].
- Shirato K, Nao N, Katano H, Takayama I, Saito S, Kato F, et al. Development of genetic diagnostic methods for novel coronavirus 2019 (nCoV-2019) in Japan. Jpn J Infect Dis. 2020;73:304–7.
- Lisowska KA, Dębska-Ślizień A, Jasiulewicz A, Heleniak Z, Bryl E, Witkowski JM. Hemodialysis affects phenotype and proliferation of CD4-positive T lymphocytes. J Clin Immunol. 2012;32:189–200.
- Katagiri D, Ishikane M, Ogawa T, Kinoshita N, Katano H, Suzuki T, et al. Continuous renal replacement therapy for a patient with severe COVID-19. Blood Purif. 2020;11:1–3.
- Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020;323:1843–4.
- Tsuchida K, Yoshimura R, Nakatani T, Takemoto Y. Blood purification for critical illness: cytokines adsorption therapy. Ther Apher Dial. 2006;10:25–31.
- van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020;382:1564–7.
- US Centers for Disease Control and Prevention. Recommendations for preventing transmission of infections among chronic hemodialysis patients. MMWR Recomm Rep. 2001;50(RR-5):1–43 .
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Suggested citation for this article: Okuhama A, Ishikane M, Katagiri D, Kanda K, Nakamoto T, Kinoshita N, et al. Detection of SARS-CoV-2 in hemodialysis effluent of patient with COVID-19 pneumonia, Japan. Emerg Infect Dis. 2020 Nov [date cited]. https://doi.org/10.3201/eid2611.201956
Original Publication Date: July 30, 2020
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