key: cord-0744154-uruklzls
authors: Ma, Yiqiong; Diao, Bo; Lv, Xifeng; Zhu, Jili; Chen, Cheng; Liu, Lei; Zhang, Sihao; Shen, Bo; Wang, Huiming
title: Epidemiological, clinical, and immunological features of a cluster of COVID-19 contracted hemodialysis patients
date: 2020-06-09
journal: Kidney Int Rep
DOI: 10.1016/j.ekir.2020.06.003
sha: a0e39e50260c04868a5ffdd4c456ecbf3fe1b70e
doc_id: 744154
cord_uid: uruklzls

BACKGROUND: The outbreak of highly contagious COVID-19 has posed a serious threat to human life and health, especially for those with underlying diseases. However, the impact of COVID-19 epidemic on HD center and HD patients has not been reported. METHODS: We reviewed the whole course of the COVID-19 in the HD center of Renmin Hospital, Wuhan University (from January 14, 2020 till March 12, 2020). We compared the clinical manifestation and immune profiles among different patient groups with healthy individuals. RESULTS: 42 out of 230 HD patients (18.26%) and 4 out of 33 medical staff (12.12%) were diagnosed with COVID-19 during the study period. 15 HD patients (6.52%), including 10 COVID-19 diagnosed, died. Only 2 deaths of the COVID-19 HD patients were associated with pneumonia/lung failure, others were ascribed to cardiovascular/cerebrovascular diseases or hyperkalemia. Except for 3 patients who were admitted to ICU for severe condition (8.11%), including 2 dead, most COVID-19 diagnosed patients presented mild or non-respiratory symptoms. The flow cytometric analysis of peripheral blood showed that multiple lymphocyte populations in HD patients were significantly decreased. HD patients with COVID-19 even displayed more remarkable reduction of serum inflammatory cytokines than other COVID-19 patients. CONCLUSIONS: Compared with the general population, HD patients and health care professionals are the highly susceptible population and HD centers are high risk area during the outbreak. A majority of HD Patients with COVID-19 exhibited mild clinical symptoms and did not progress to severe pneumonia likely due to the impaired cellular immune function and incapability of mounting cytokines storm. More attention should be paid to prevent cardiovascular events, which may be the collateral impacts of COVID-19 epidemic on HD patients.

Since December 2019, the initially outbreak of COVID-19 in Wuhan city has 2 spread rapidly to all over China and even the world, becoming a serious pandemic 3 [1-4]. As of March 12, 2020, the total laboratory-confirmed COVID-19 cases in 4 Wuhan city, nationwide of China, and world globally reached to 49,986, 80,981, and 5 125,260 respectively [5, 6] . Epidemiological data suggest that COVID-19 patients 6 with underlying conditions such as diabetes, hypertension, cardiovascular disease or 7 the elderly are at a higher risk of mortality [7, 8] . Considering the large population size In this study, we reviewed an outbreak of COVID-19 in the HD center in Renmin 13 Hospital of Wuhan University, one of the largest hospitals in Wuhan city. A cluster of 14 HD patients who contracted COVID-19 were surveyed since January 14, 2020, the 15 day when the first case was confirmed, and followed until the day on March 12, 2020. 16 The epidemiological, clinical, laboratory, and radiological characteristics, and 17 outcomes of some of these patients were reviewed. We expect our findings will shed 18 light on the appropriate management of the HD center and HD patients in face of 19 COVID-19 or other similar epidemic emerging. Health Commission of China [12] [13] [14] . In the 5 th edition, the suspect case of 2 COVID-19 is defined as the one has the epidemiological history or clinical 3 presentations of fever, respiratory symptoms, or decreased white blood cells or The medical records of all participants were analyzed by the research team.

Epidemiological, clinical, laboratory, and radiological characteristics and outcomes 20 data were obtained with data collection forms from electronic medical records or 21 specific data questionnaire. Some data were retrieved from the Hubei Province kidney 22 disease quality control information platform. Information collected including 23 demographic data, medical history, underlying comorbidities, symptoms, signs, blood 24 tests and chest computed tomographic (CT) scans. During the period of follow up, the 25 odd episode of death happened among these patients were recorded and the cause of 26 death were carefully evaluated by the research team, based on the time, place and 27 clinical manifestation of the death.

The SARS-CoV-2 detection was done by real-time PCR (RT-PCR) as described 1 previously [15] . Briefly, nasopharyngeal swab samples of participants were collected 2 for SARS-CoV-2 test with the detection kit (Bioperfectus, Taizhou, China). The 3 ORF1ab gene (nCovORF1ab) and the N gene (nCoV-NP) were used for real-time 4 RT-PCR according to the manufacturer's instructions. Reaction mixture were prepared 5 and RT-PCR assay was then performed under the following conditions: incubation at 6 50 °C for 15 minutes and 95 °C for 5 minutes, 40 cycles of denaturation at 94°C for 7 15 seconds, and extending and collecting fluorescence signal at 55 °C for 45 seconds. The measured data were using median and interquartile range (IQR) values and 27 compared using independent group t test. Enumeration data were described as number 28 (%). All statistical analyses were performed using SPSS (Statistical Product and significant difference. 

Patient characteristics and study design 4 230 patients and 33 staff in our HD center were included in this study. The 5 cumulative incidence of COVID-19 epidemic in our HD center is presented in Figure   6 1(A). The first COVID-19 patient was diagnosed on January 14, and the second 7 diagnosed patient appeared on January 17. On January 19, a nurse was confirmed as 8 the first infected medical staff in our HD center. Since January 21, patients with 9 COVID-19 had been quarantined and all medical staff had been asked to upgrade their 10 personal prevention and protection, which including wearing full protective gear such 11 as waterproof disposable gown, cap, gloves, face shield, and N95 face mask, and 12 more rigorous cleaning and disinfection. Two days later, 2 medical staff were 13 diagnosed. On February 4 th , 2 new patients were further confirmed with COVID-19.

14 Therefore, the HD center decided to screen all patients and staff with chest CT and Table 1 . All of the deaths were followed and reviewed by our research team, except 16 2 patients died in ICU (Table 1) Table 2 . common in COVID-19 patients as previous reports [7, 8, 16, 17] . These features were 1 also present in the COVID-19 contracted HD patients (Table 3) . Anemia was also 2 commonly seen in these patients, but primarily ascribed to ESRD complications. With 3 respect to the clinical symptoms in HD patients with COVID-19, we found that only 2 4 (13%) in confirmed diagnosed, and 2 (7%) in clinically diagnosed patients had fever, 5 or fatigue. Three patients had the symptom of dry cough and only one clinically 6 diagnosed patient had chest pain. One confirmed diagnosed and one clinically 7 diagnosed patient had nausea. Most of the patients present no obvious symptoms 8 (Table 3) . Radiological examination by chest CT scan showed that 2 (13%) confirmed 9 diagnosed patients and 8 (30%) clinically diagnosed patients had unilateral cytokines. This "cytokine storm" effects are responsible for severe conditions or even 26 eventually lead to death of COVID-19 patients [16] . As we mentioned earlier, most of 27 the HD patients with SARS-CoV-2 infection were showed relatively mild symptoms. 28 We speculated that this might be related to the compromised immunity in HD patients.

To test this hypothesis, we enumerated the absolute numbers of T cells, NK cells, as well as B cells in PBMCs of HD patients in the presence of absence of SARS-CoV-2 1 infection. We found that the numbers of T cells, CD4 + T cells, CD8 + T cells, NK cells 2 and B lymphocytes in PBMCs of HD patients were significantly lower compared with 3 those of non-HD patients. These numbers in HD patients with SARS-CoV-2 infection 4 were further decreased (Table 6 and Figure 2(A) ). Similar to the numbers of 5 lymphocytes, we also observed that the serum levels of IL-4, IL-6, and TNF-α in non 6 HD patients with SARS-CoV-2 infection were significantly higher than the normal 7 level, while the serum levels of these cytokines in HD patients with or without 8 SARS-CoV-2 infection are significantly lower than those in non HD patients with 9 SARS-CoV-2 infection (Table 7 and Figure 2(B) ). These results suggest that HD 10 patients have compromised immune system, which may be detrimental for mounting 11 effective anti-viral responses, but beneficial for limiting tissue damages by dampening 12 the cytokine release. control. According to our investigation on single center, the infection rate of HD 2 patients in the COVID-19 epidemic is indeed much higher than that of other 3 population, and the staffs in HD center are also at high risk to infection.

Reviewing the epidemic situation in our center can bring some important 5 experiences and lessons which have been described elsewhere [21] [22] . The 6 COVID-19 epidemic initially emerged in our center on January 14, 2020, and the first 7 infected medical staff appeared on January 19, 2020, but until January 21, actions 8 were taken by our center to stand up to, we must admit that the best time has missed. 9 Nevertheless, series of measures including upgrading prevention and protection, 10 quarantine and isolation, seem to be effective to contain the epidemic, but the most 11 critical means we think is thoroughly finding out the infected cases by repeated 12 screening, which is mainly based on the results of chest CT scan. The suspected 13 infection with abnormal radiological images were further subjected to SARS-CoV-2 14 nuclear acid test. Once the diagnosis of COVID-19 being made, the patient will be 15 transferred to the designated hospital within 4 hours according to the contingent plan.

Other issue needs to be noted is that the outbreak of COVID-19 in our center left 13 17 death, with a mortality of 5.65%, which is far higher than that of the same period in 18 history. The major causes of deaths were cardiovascular and cerebrovascular 19 complications or hyperkalemia rather than pneumonia, the real reason we speculated 20 was inadequate dialysis. It's not worth it to avoid infection by reducing the frequency 21 of dialysis, since COVID-19 infection in HD patients seemed to less severe or fatal. 

NK cells (/μl) 99

B cells (/μl)