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      Infection Control Precautions and Care Delivery in Hemodialysis Unit during Coronavirus Disease 2019 Outbreak: A Case Series

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          Abstract

          Background

          With an estimated basic reproductive number of 3.77, the Coronavirus Disease 2019 (COVID-19) continues to spread. It is urgent to exert adequate efforts for the management of dialysis patients, caregivers, and healthcare personnel (HCP). This study aimed at reporting practical workflow, identification of high-risk or suspected cases of CO­VID-19, and subsequent response measures.

          Methods

          At the time of the COVID-19 outbreak, precautions and practice protocols were applied in our dialysis units (DUs). This single-center study retrospectively reviewed all high-risk/suspected cases from January 23, 2020, to February 10, 2020. Epidemiological, clinical feature, and detailed data on all cases were recorded.

          Results

          Practical workflow for the clinical management of dialysis patients, caregivers, and HCP was initiated. A total of 6 high-risk/suspected cases were identified. Female gender, older age, presence of cardiovascular disease, diabetes, anuresis, immunocompromised status, hypoalbuminemia, and underweight were noticeable features in these cases. Direct evidence of infection or epidemiological risk was detected in five cases. Close monitoring for temperature and oxygen saturation during hemodialysis sessions may be reasonable. No confirmed COVID-19 cases were reported in our DU, but certain cases showed rapid deterioration due to other critically severe condition needing hospitalization. Portable dialysis machines are of great need to ensure dialysis care provision.

          Conclusions

          Our study described a practical workflow for patient-centered management during COVID-19 outbreak. Potential risk factors and underlying clinical patterns were reported. Further studies regarding the efficacy of infection control precautions and practice protocols tailored for dialysis settings are warranted.

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          Most cited references 13

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          Hospital outbreak of Middle East respiratory syndrome coronavirus.

          In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care-acquired MERS-CoV infections. Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced. Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases). Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.
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            Caution on Kidney Dysfunctions of 2019-nCoV Patients

             Zhen Li,  Ming Wu,  Jie Guo (2020)
            Until 24:00 of February 7th 2020, 31774 laboratory-confirmed cases of novel coronavirus (2019-nCoV) infection have been reported, including 6101 severe cases in critical conditions and 722 deaths. The critical and urgent need at this moment is to find an effective treatment strategy with available means to prevent these thousands of severe inpatients from worsening and dying. It has been recently known that the 2019-nCoV shares a common cellular mechanism with the severe acute respiratory syndrome-associated coronavirus (SARS-CoV). Thus, we surveyed a previous retrospective case study on SARS which showed that acute renal impairment was uncommon in SARS but carried a formidably high mortality (91.7%, 33 of 36 cases). Here we report an ongoing case study on kidney functions in 59 patients infected by 2019-nCoV (including 28 diagnosed as severe cases and 3 deaths). 63% (32/51) of the patients exhibited proteinuria, indicative of renal impairment. 19% (11/59) and 27% (16/59) of the patients had an elevated level of plasma creatinine and urea nitrogen respectively. The computerized tomography (CT) scan showed radiographic abnormalities of the kidneys in 100% (27/27) of the patients. Together, these multiple lines of evidence point to the idea that renal impairment is common in 2019-nCov patients, which may be one of the major causes of the illness by the virus infection and also may contribute to multi-organ failure and death eventually. Therefore, we strongly suggest exercising a high degree of caution in monitoring the kidney functions of 2019-nCoV patients and, very importantly, that applying potential interventions including continuous renal replacement therapies (CRRT) for protecting kidney functions as early as possible, particular for those with plasma creatinine rising, is key to preventing fatality.
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              Coronavirus Epidemic and Extracorporeal Therapies in Intensive Care: si vis pacem para bellum

              The worldwide outbreak of coronavirus disease 2019 (COVID-19) has demonstrated that we are all part of a small world where diffusion of contagious diseases is inevitable [1]. Although the new coronavirus originated in Wuhan seems to present lower lethality compared to previous epidemic outbreaks from other coronaviruses, its capacity of diffusion has been phenomenal [2, 3]. One infected individual may transmit the virus to 2 or 3 others [4]. Of note, screening based on symptoms and signs is ineffective and asymptomatic persons can spread the disease [5]. In the very early phases, before this wide diffusion of the virus, a call to action was published in Lancet Respiratory Medicine [6] underlining the need of alertness for zoonotic virus infections crossing species and infecting human populations [7]. In particular, recommendation was made to prepare intensive care teams to deliver extracorporeal organ support (ECOS) therapies in infected patients whose pulmonary syndromes are particularly severe [8]. Once again, despite previous experiences presented higher incidence of severe complications and lethality, the current outbreak still requires intensive care for 5% of the infected population. Among those critically ill patients, the mortality rate is 49%. Even with the specific tropism for airway epithelial cells, the infection seems to be weak in humans and transmission is likely to occur only when lower respiratory tract disease develops. COVID-19 causes mild flu-like symptoms or even no symptoms in the majority of the patients [3]. Coronaviruses bind to receptors such as angiotensin-converting enzyme 2. Angiotensin-converting enzyme 2 is present in the epithelia of the lung, small intestine, colon, and biliary tract. In fact, viral nucleic acids were found in stools and anal swabs of patients diagnosed with COVID-19 infection [9]. In a cohort of COVID-19-infected patients from Singapore, half (4 out of 8) of patients tested had the virus detected in stools [10]. This might explain liver dysfunction, diarrhea, nausea, and vomiting that occurred in patients with pneumonia, namely, the gut-lung crosstalk [8, 11]. In a Chinese group of patients with pneumonia caused by COVID-19, 23% were admitted to intensive care unit (ICU), 17% had acute respiratory distress syndrome, and 11% died [11]. Major preventive measures have been undertaken in specific areas where the incidence was significantly higher, to limit the diffusion of the virus [7]. Despite those measures, the requirement of ICU services and stations still has dramatically increased. Personal communications and early reports mostly coming from China suggest that 67% of severely ill COVID-19 patients may present with additional organ dysfunction syndromes [8, 11, 12]. This has been, at least in part, related to a sepsis-like syndrome induced by high level of circulating cytokines [2, 12]. In such circumstances, while pulmonary exchanges are compromised and dominate the clinical scenario, acute kidney injury and heart and liver dysfunction may also become evident [8, 12, 13, 14]. Cytokine storm may be induced by a superimposed septic syndrome or by the direct effect of the virus on the infected host. In the past, the experience matured with H1N1 influenza, SARS, and MERS has suggested that the severity of illness depended on comorbidities and the immune-competence of the individual. In severe situations, however, an uncontrolled inflammatory state or a subsequent/simultaneous immune-paralysis is the direct consequence of endocrine effects of pro- and anti-inflammatory cytokines spilled over into the systemic circulation. Of special interest, in a retrospective analysis of a German cohort [15] of 25 critically ill H1N1-infected patients, the prevalence of virus-associated hemophagocytic syndrome (VAHS) was 36%. All patients with the syndrome had received extracorporeal membrane oxygenation (ECMO). ECMO could have been a trigger or an amplifier of cytokine activation. The pathogenesis of VAHS involves excessive production of interferon gamma and interleukin-2 [16]. VAHS itself is a prototype of a cytokine storm syndrome. In our present experience in San Bortolo Hospital, all our 4 COVID-19 critically ill patients have hyperferritinemia, raising awareness of VAHS as a differential diagnosis. In organ dysfunction syndromes when pharmacological treatment is simply not available or efficacious, mechanical ventilation and hemodynamic support seem to be the only possible therapeutic strategy [17]. However, extracorporeal therapies such as hemofiltration or hemoperfusion (HP) offer a new possibility to support different organs in a multiple organ dysfunction condition. Using specific extracorporeal circuits and devices, heart, lungs, kidneys, and liver can be partially replaced or at least sustained during the severe phase of the syndrome. The concept is known as ECOS [18, 19, 20]. The most important technique in these cases is the ECMO mostly applied in veno-venous mode [21, 22, 23]. Furthermore, extracorporeal CO2 removal is another option that can be performed in less severe cases to facilitate a less invasive and traumatic mechanical ventilation [24]. Although acute kidney injury in these patients is not common, continuous renal replacement therapies may offer in conditions of mild to severe kidney dysfunction a significant support for solute and fluid control. The same is true for left ventricular assist devices in case of refractory heart failure or albumin dialysis and HP in case of liver dysfunction and hyperbilirubinemia [25]. However, according to information collected from Chinese colleagues who faced a large proportion of patients with complicated COVID-19 syndromes in their ICUs, a significant benefit seems to have been obtained with the use of direct HP with cartridges containing highly biocompatible sorbents and microporous resins [26]. Such therapies, designed to remove the excess of circulating cytokines, seem to have displayed a remarkable benefit in terms of hemodynamic support and organ function recovery [2]. The suggested scheme of application of HA380 cartridges (Jafron Biomedical Co., China) was 2-1-1, that is, 2 units utilized for 12 h in the first 24 h and 1 unit per day utilized for 24 h in the following 2 days. In Europe, we had matured some experience with the use of Cytosorb© cartridges (CytoSorbents Corporation, NJ, USA), exactly for the same purpose of controlling deadly inflammation in critically ill and cardiac surgery patients [27, 28]. This approach may be just one of many others [29] utilizing extracorporeal therapies in these severe syndromes and will require scientific validation once the emergency of the current epidemic will be over. The suggested mechanism is the nonspecific removal of the peaks of the circulating cytokines both in the pro- and in the anti-inflammatory side. This is consistent with the “peak concentration hypothesis” suggested some time ago [30]. In presence of our inability to obtain instantaneous monitoring of biological levels of cytokines, the reasonable approach is to promote a nonspecific removal assuming that those cytokines with the highest concentration will be removed in higher amount (Fig. 1) [31]. This would facilitate a return to a less severe derangement of the immune system and to an improved level of the immunological response of the host. The same concept has been expressed by the “cytokinetic model.” In this theory, the reduction of circulating levels of cytokines may allow the immune system of the patient to redirect the immunocompetent cells to the source or site of inflammation [32]. We warn users of these techniques that together with the removal of cytokines, some drugs and antibiotics like vancomycin are also removed. In vitro models proved that [33]. In this case, a specific adjustment of antibiotic dosage in patients with bacterial infections should be carefully planned. Another adjunctive potential extracorporeal therapy is lectin affinity plasmapheresis for coronavirus trapping. Blood runs into a plasma filter, and the filtered plasma containing viral copies passes through a matrix of lectins. There is a high affinity between the viral envelope and lectins. Likewise, some viral copies are captured and the viremia is reduced [34]. This therapy should be further explored and validated. The main message the present editorial tries to convey is that the ICU staff and treating physicians should be familiar with the concept that extracorporeal therapies represent today an important strategy in critically ill patients with multiple organ dysfunction. Training and research should be planned to further develop skills and knowledge in this area where new membrane separation processes and adsorption techniques appear to be a new frontier in fighting the so-called “cytokine storm syndrome.” We will need to increase awareness of the basic principles, to study mechanisms, to optimize prescription and delivery of different techniques. We need to stimulate research and data collection to create sufficient scientific evidence. We need to prepare for the uncertain future where the frequency of these crises will be probably increasing [4]. We must retool ourselves with new strategies and new therapies, and among those, new ECOS therapies. As the ancients used to say: “Si vis pacem, para bellum,” if you want peace, get prepared to war. Disclosure Statement The authors have no conflicts of interest to declare. Funding Sources There are no funding sources to declare. Author Contributions All authors contributed equally to the manuscript and approved submission.
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                Author and article information

                Journal
                Blood Purif
                Blood Purif
                BPU
                Blood Purification
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                0253-5068
                1421-9735
                5 June 2020
                : 1-8
                Affiliations
                aDepartment of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
                bDepartment of Hospital Infection, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
                Author notes
                *Hong-Zhen Ma, Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54 You-Dian Road, Hangzhou 310006 (China), hongzhenmapresent@ 123456126.com
                Article
                bpu-0001
                10.1159/000507876
                7316656
                32506055
                Copyright © 2020 by S. Karger AG, Basel

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                Page count
                Figures: 2, Tables: 2, References: 26, Pages: 8
                Categories
                Research Article

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