key: cord-339471-1510mzmy
authors: Ikizler, T. Alp
title: COVID-19 in Dialysis Patients: Adding a Few More Pieces to the Puzzle
date: 2020-05-08
journal: Kidney Int
DOI: 10.1016/j.kint.2020.04.032
sha: 
doc_id: 339471
cord_uid: 1510mzmy

The clinical presentation and mortality rate in maintenance hemodialysis (MHD) patients with COVID-19 are not well established. Recent data from Italy and Spain suggest that these patients present with wide range of symptoms, with a significant portion being asymptomatic. There is prolonged positivity of pharyngeal swabs in MHD patients. The mortality rates are very high, reaching almost 30%. These data highlight the importance of diligent oversight and care of MHD patients during COVID-19 pandemic.

Maintenance hemodialysis (MHD) patients are at increased risk for COVID-19 and its complications due to presence of multiple co-morbid conditions. The logistical aspects within a dialysis facility further increase the risk of disease transmission 1 . Despite these obvious concerns, early reports from the epicenter of the disease, Wuhan, Hubei Province in China suggested that the incidence of COVID-19 was lower than expected with potentially milder course and outcomes in MHD patients. With the expansion of the pandemic to Western Europe, more data are emerging regarding the impact of this disease on MHD patients. In this issue of the journal, three special reports from United Kingdom, Italy and Spain provide preliminary information that offer some clues to the puzzle.

In a Letter to the Editor, Dudreuilh et al 2 provide the results of serial SARS-CoV-2 swabs testing performed 7 days after a confirmed Covid-19 diagnosis in 34 MHD patients. Only 5 patients cleared the virus in less than 11 days and by day 15, 14 patients (41%) had not cleared the virus. They noted that it is not known whether detection of viral RNA represents the ability to transmit the virus in these patients but there is clear precedent to continue to isolate them in the dialysis facility.

In a special report, Alberici et al 3 describe their clinical experience with MHD patients cared at four outpatient dialysis facilities that are part of "Brescia Renal COVID task force". While 3 units tested only symptomatic patients, one unit tested all patients. In a period of one month, viral positivity was detected in 94 of their 643 MHD patients (15%). The positivity rates were not substantially different between the two screening approaches (14% versus 16%, respectively). Patients who tested positive were either managed as outpatients (39%) or hospitalized (61%), based on disease severity assessed by a clinician. Prominent findings in the study were the mild form of symptomatology at presentation, the high rate of overall mortality (29%) and emergence of usual risk factors for mortality and ARDS in SARS-CoV-2 positive MHD patients. In addition, while certain patients were deemed more stable and managed in the outpatient facility, 3 of those subsequently died and a substantial portion had significant worsening of their symptoms.

In another special report, Goicoechea et al 4 describe the clinical course and outcomes of 36 patients from two dialysis facilities caring for 282 patients that were admitted to a tertiary hospital in Madrid based on positive RT-PCR for SARS-CoV-2. They report a mortality rate of 30.5%, and 33% of their patients required mechanical ventilation. While the patients were identified by a variety of symptoms on admission, the ones who had a worsening of their respiratory status, clinically or radiologically, had much worse outcome. They further note that high LDH and C-reactive protein (CRP) concentrations on day 7 after admission were also predictive of higher mortality in their cohort. Patients were treated with a wide range of medications. Although the authors note a signal suggesting that treatment with azithromycin and corticosteroids might be associated with lesser mortality, there are multiple confounders along with changes in management protocol during the observation period which preclude any firm conclusions.

Taken together, these three early reports provide important information regarding the clinical course of COVID-19 in MHD patients. First and foremost, while MHD patients might present with a wide range of symptom severity, the clinical outcomes, especially mortality rates, are dramatically high in this vulnerable patient population, reaching almost 30%. In the report by Alberici et al, itis noteworthy that even in MHD patients who were deemed to be stable and managed as outpatients, there were ones whose clinical condition abruptly worsened leading to subsequent death. This high mortality rate is far greater than what was published this year and more consistent with what would be expected in a cohort with underlying co-morbidities that are associated with poor outcomes. MHD patients also had significant pulmonary complications with high percentages of ARDS and mechanical ventilation suggesting that MHD patients are at very high risk of COVID-19 complications and should be managed accordingly.

The report by Dudreuilh et al highlights another perspective of disease spectrum in MHD patients, namely the prolonged viremia. While, as noted astutely by the authors, it is not known yet whether the persistent viremia represents the ability to transmit the virus or not, it does reemphasize the need for stringent oversight in management of MHD patients with COVID-19 until the relationship between presence of viral RNA in swabs and risk for transmission is further clarified.

The future implications of these preliminary reports are multiple. Given the severe course of disease and poor outcomes, it seems prudent that MHD patients be included in the high-risk populations that are continuously and repetitively tested for screening purposes such as ones that reside in nursing homes. Currently, the capability to screen subjects with or without symptoms differs amongst countries and regions. However, allocating screening resources to dialysis patients is a potential opportunity to utilize these resources wisely. This will allow early isolation of patients with positive tests, improve staff and patient protection by minimizing potential transmission within a dialysis facility and direct precious resources to individuals in most need.

Another interesting aspect of these reports is the wide range of symptoms in MHD patients tested positive for SARS-CoV-2, with a significant portion being asymptomatic. It is yet unclear whether this reflects the disease spectrum itself or a phenomenon related to underlying advanced kidney disease. The uremic state is well known to be associated with impaired immune response potentially leading to reduced fever occurrence during infection. However, other symptoms of COVID-19 such as cough, shortness of breath and fatigue are inherently present in maintenance dialysis patients and could be under reported by most patients, potentially leading to misdiagnosis. Given the grave nature of disease in these patients, reliance on symptoms for diagnosis and management of COVID-19 could be detrimental and further highlights the absolute need for universal testing for screening purposes in maintenance dialysis patients.

Despite their informative nature, these reports must be interpreted with ((some significant)) caution. Most importantly, these data are descriptive and lack appropriate controls for precise estimations. For example, one cannot draw any conclusions whether prolonged detection of viral RNA is characteristic of advanced kidney disease or merely a reflection of other patient specific factors. It is also premature to conclude that maintenance dialysis patients have a milder clinical presentation compared to individuals of the population at large with similar clinical and demographic features 5 . Presumably, widespread universal testing in general population and high-risk patient populations would be able to answer this question more reliably. Despite the consistently high mortality rate and disease progression observed in the two studies from Italy and Spain, the actual prevalence of the disease and its diagnostic and prognostic predictors are still yet to be determined. It is also important to recognize that certain logistical reasons might have driven a higher than expected mortality rate such as overwhelmed healthcare systems as observed in Italy and Spain. Future more comprehensive studies from different geographically diverse cohorts will surely provide more complete data. Finally, these studies suggest a gunshot approach to treatment of COVID-19 in MHD patients. Given the small sample size, lack of appropriate control groups and the inconsistency and changes in treatment protocols, any conclusion about effectiveness of any of the treatment regimens should be avoided. It is also crucial to underline that these treatments should be used with great caution in MHD patients due to their altered pharmacokinetics and toxicity 6 . On the other hand, this could lead to an unintended systemic exclusion of maintenance dialysis patients from ongoing or future randomized trials despite the obvious urgency to include them due to reasons mentioned above.

Overall, the authors of these early reports must be commended for their diligent and heroic work during a devastating pandemic. These data provide early clues to the prevention and management strategies in MHD patients during the COVID-19 pandemic and potentially for future healthcare crises. In order to improve our responsiveness to emerging threats in the future, we undoubtedly need reliable and comprehensive scientific data on a timely basis.

Managing the COVID-19 pandemic: international comparisons in dialysis patients

Deisolation of COVID-positive haemodialysis patients in the outpatient setting: a single centre experience

CLINICAL CHARACTERISTICS AND SHORT-TERM OUTCOME OF HAEMODIALYSIS PATIENTS WITH SARS-CoV-2 INFECTION: THE BRESCIA RENAL COVID TASK FORCE EXPERIENCE. Kidney International

COVID-19: Clinical course and outcomes of 36 maintenance Hhemodialysis patients in Spain

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial

Alp Ikizler is a member of American Society of Nephrology COVID-19 response Team and chairs Nephrologists Transforming Dialysis Safety (NTDS) Current Emerging Threats Subcommittee. Dr. Ikizler reports receiving honorarium from Fresenius Kabi, GmbH, Abbott Renal Care and International Society of Nephrology for consulting work

The information about the impact of coronavirus disease 2019 (COVID-19) on maintenance hemodialysis (MHD) patients is evolving. The Editors recommend that the readers also view the LTE by Dudreuilh et al (XXX) reporting the results of serial SARS-CoV-2 swabs testing performed 7 days after a confirmed Covid-19 diagnosis in 34 MHD patients. Two other special reports by Alberici et al (XXX) and Goicoechea et al (XXX) provide important information about their clinical presentation and mortality rates in MHD patients diagnosed with COVID-19. Generalizability of these preliminary data needs to be confirmed in more comprehensive studies