key: cord-0955474-1e8j8qys
authors: Abe, Tatsuki; Izumo, Takehiro; Ueda, Akihiro; Hayashi, Munehiro; Ishibashi, Yoshitaka
title: Successful treatment of two Japanese ESRD cases with severe COVID-19 pneumonia
date: 2020-07-26
journal: CEN Case Rep
DOI: 10.1007/s13730-020-00512-7
sha: 601db751e0562dd092facbdb0bf1224bca7bf045
doc_id: 955474
cord_uid: 1e8j8qys

Novel coronavirus disease 2019 (COVID-19) is a highly infectious and deadly disease, spreading worldwide. There are limited data about the clinical course of end-stage renal disease (ESRD) patients infected with COVID-19. However, previous cohort studies showed a high mortality rate of ESRD patients infected with COVID-19. We report here two Japanese ESRD patients confirmed with severe COVID-19 pneumonia. Case 1 was a 60-year-old man with ESRD due to diabetic nephropathy who were infected with COVID-19 and exhibited acute respiratory distress syndrome (ARDS) requiring mechanical ventilation and intensive care unit (ICU) admission. He was treated with tocilizumab and intravenous immunoglobulin (IVIG). After 6 days of treatment in ICU, he was extubated. Case 2 was a 68-year-old woman undergoing maintenance hemodialysis for 17 years who also exhibited ARDS due to COVID-19. Her clinical course resembles case 1. Our experience of these two cases indicates that anti-cytokine therapy might be effective for severe COVID-19 pneumonia in ESRD patients.

Since December 2019, the current outbreak of novel coronavirus disease 2019 (COVID-19) has spread to many countries including Japan. Some previous studies revealed the clinical characteristics of patients infected with COVID-19 [1] . However, there are limited reports about the clinical course of end-stage renal disease (ESRD) patients infected with COVID-19. We report here 2 Japanese patients with ESRD, who recovered from severe COVID-19 pneumonia.

A 60-year-old man with ESRD due to diabetic kidney disease (DKD) presented with 4 days of cough, slight fever and fatigue. On admission, his temperature was 37.7 °C with an oxygen saturation of 98% in room air. Laboratory tests revealed an increased level of blood urea nitrogen, creatinine, CRP, ferritin, soluble IL-2 receptor and D-dimer, and decreased lymphocyte count (Table 1) . A chest CT scan showed bilateral and peripheral ground-glass opacities (GGO) in the lung (Fig. 1a) . A nasopharyngeal swab for RT-PCR was positive for COVID-19, he was diagnosed as COVID-19 pneumonia. Then, he was treated with ceftriaxone, azithromycin, peramivir and favipiravir. Hemodialysis (HD) was started on day 3. His pneumonia was gradually getting worse after the first session of HD. His body temperature rose above 38 °C and his oxygen requirements increased day by day. A CT scan showed the area of GGO expanded on day 4 (Fig. 1a) . Given his hyper-inflammatory status with elevated IL-6 (47.8 pg/mL), the patient was administered 8 mg/kg of tocilizumab twice and 2500 mg of intravenous immunoglobulin (IVIG) twice. No concomitant drugs such as antihistamine agents were used with tocilizumab and IVIG. On day 6, he exhibited acute respiratory distress syndrome (ARDS) with PaO 2 /FiO 2 ratio of 133, and he was transferred to the intensive care unit (ICU) and intubated. During 6 days of treatment in ICU, his fever fell below 37 °C on day 7, his hemodynamic status was stable, PaO 2 /FiO 2 ratio was gradually improved to 310 on day 9, and the level of CRP decreased (Fig. 1b) , suggesting that his pneumonia was improved. He was extubated on day 12. Because of the negative results of RT-PCR assay, he was released from the isolation unit on day 29. He didn't recover from incident hemodialysis.

A 68-year-old woman on HD for 17 years due to DKD was referred to our emergency department with a chief complaint of fever, cough, and diarrhea. Her body temperature was 38.6 °C with an oxygen saturation of 96% in room air. Laboratory tests revealed similar results as with case 1 (Table 1) . A nasopharyngeal swab for RT-PCR was positive for COVID-19. Her clinical course after admission resembles that of case 1. She was treated with azithromycin, meropenem, and peramivir immediately. On day 3, her pneumonia was rapidly getting worse. Her oxygen requirements acutely increased to 6 L/min via a non-rebreather mask with PaO 2 of 140 in the night, meaning she developed ARDS. On day 4, she was intubated and treated in an intensive care unit with (Fig. 2b) . Finally, she was extubated and returned from ICU on day 9. She was released from the isolation unit on day 36 based on negative results of PCR assays.

We have experienced two Japanese ESRD patients who recovered from severe COVID-19 pneumonia. This is the first time to report in detail the clinical course of ESRD patients, who recovered from severe COVID-19 pneumonia. Our patients had diabetes and hypertension, risk factors for severity [1] . Previous cohort studies showed ESRD was also related to aggravation [2, 3] . Trujillo In the first phase, the patients are asymptomatic or present with flu-like symptoms. Antiviral therapy including favipiravir would be a therapeutic option. In the second phase, the patients exhibited a hyperinflammatory status called cytokine storm. Therefore, immunosuppressive therapy might be therapeutic options. Tocilizumab, a humanized monoclonal antibody against IL-6 receptor, and IVIG were reported to be options [4, 5] . We used these drugs quickly when the patients exhibited ARDS. These drugs might exert a protective effect against the development of ARDS. In fact, after administration of these drugs, C-reactive protein started to decrease to normal range in 2 weeks (Fig. 1b) . It coincided with the recovery from ARDS. Therefore, early treatment may lead to improved survival even for ESRD patients.

In conclusion, we described two ESRD patients, who fully recovered from severe COVID-19 pneumonia. The recovery might be attributed to the usage of tocilizumab and IVIG in the early phase of progressive disease.

Acknowledgements We thank both patients and all involved doctors. Fig. 2 a A chest computed tomographic image and chest X-rays of case 2. A CT scan showed bilateral and peripheral ground-grass opacities (GGO) on day 1. The GGO on X-rays expanded especially through day 1 to day 7. On day 15, the area of GGO was reduced. b Clinical course of case 2. As with case 1, the level of CRP decreased and PaO 2 /FiO 2 ratio was improved after the administration of tocilizumab and IVIG

Clinical characteristics of coronavirus disease 2019 in China

SARS-CoV-2 infection in hospitalized patients with kidney disease

Management of patients on dialysis and with kidney transplant during SARS-COV-2 (COVID-19) pandemic in Brescia

Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in

SARS-CoV-2 infection complicated by inflammatory syndrome. Could high-dose human immunoglobulin for intravenous use (IVIG) be beneficial?

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Conflict of interest All the authors have declared no conflict of interest.Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.Informed consent Informed consent was obtained from all individual participants included in the study.