COVID-19 and Dialysis Patients

Introduction

This is a point-in-time view of early pandemic. While the principles remain the same, the facts of COVID-19 care have evolved since 2020. Through August 2020, COVID-19 disease caused by the novel coronavirus SARS-CoV-2 has infected more than 30,500,000 people worldwide and caused nearly 1,000,000 deaths. The virus enters host cells via angiotensin-converting enzyme 2 (ACE-2) receptors, highly expressed in the mouth, tongue, and lower lung types I and II alveolar epithelial cells. ACE-2 receptors are expressed in target organs for SARS-CoV-2, including kidney proximal tubular cells and podocytes, cardiac endothelial cells, gut enterocytes, and blood vessels. Inhibitors of the renin-angiotensin system are common treatments for hypertension in patients with chronic kidney disease (CKD). While initial studies suggested that these agents might increase ACE-2 receptor expression, data do not support an association with COVID-19. Several possible mechanisms have been proposed for acute kidney injury (AKI) in the setting of COVID-19 infection, including prerenal injury resulting from high fever, gastrointestinal (GI) losses, and decreased oral intake; cardiac complications like cardiomyopathy or cardiorenal syndrome leading to renal hypoperfusion; toxic tubular damage due to intense production of proinflammatory cytokines leading to decreased renal perfusion and tubular injury over time; direct viral entry into kidney cells leading to tubular damage; and a hypercoagulable state leading to thrombotic microangiopathy.

Published reports document risk factors for COVID-19 infection, including hypertension (odds ratio [OR], 2.29), diabetes mellitus (OR, 2.47), and cardiovascular disease (OR, 2.93), all of which are common among patients with CKD. Increasing age, obesity, and the black race also increase the risk of infection. Minorities and older patients are disproportionately represented in the population of patients with CKD: 23% of incident patients are older than 75, 26% are black, and 15% are Hispanic. Patients requiring maintenance dialysis have a much higher rate of infection when treated by in-center hemodialysis (HD) compared to home dialysis therapies. The risk of mortality increases as CKD progresses; 15%–40% of patients with CKD requiring maintenance dialysis who are infected by COVID-19 die. Mortality is greater in those with hypertension, diabetes mellitus, and cardiovascular disease, as well as older and black patients.

Initial symptoms of COVID-19 may be milder in patients with CKD: fatigue, cough, and dyspnea are reported less frequently; hypoxemia is less apparent because of reduced oxygen levels at baseline, and fever is less common because of reduced baseline body temperature. Diarrhea and fatigue are more common in patients with CKD. Many patients present asymptomatically for HD but develop a fever during treatment and are subsequently diagnosed with COVID-19. Patients with CKD have higher levels of creatine kinase, myoglobin, troponin I, B-type natriuretic peptide, and procalcitonin than those with normal kidney function.

The impact of COVID-19 on the population of patients receiving maintenance dialysis is not yet known: will the high mortality rate be balanced by the number who initiate renal replacement therapy (RRT) as a result of AKI associated with COVID-19? Similarly, the impact of COVID-19 on the nephrology workforce is not yet known; some will retire because of the physical and emotional impact of COVID-19, but new personnel may be attracted by the opportunities the field presents to care for patients with chronic illness throughout their life cycle and the opportunity to impact the outcomes of patients with severe acute illness.

Patients

A major tool to prevent infection spread during the SARS-CoV-2 pandemic is social distancing. Maintaining at least 6 ft of separation between individuals is virtually impossible for patients receiving in-center HD, where they are often tightly clustered at the dialysis center and during transportation from home. In spite of the risk, patients must continue to receive life-sustaining dialysis treatments. Infection “hotspots” developed early during the COVID-19 pandemic in New York, Chicago, Detroit, and other cities. Hospitals were quickly overwhelmed, precluding the possibility of sending patients with suspected or confirmed COVID-19 and mild symptoms to the hospital for dialysis management. Patients with known SARS-CoV-2 infection or those suspected to be infected (patients under investigation or PUIs) had to be treated in the outpatient setting. Some centers shortened dialysis treatments or decreased their frequency to minimize the risk of no social distancing, but concerns arose quickly about the risk of adverse outcomes of reduced dialysis adequacy. Exposure to COVID-19 was reduced by furlough of infected staff and by cohorting infected patients and PUIs in facilities treating only patients with active or suspected infection or on separate shifts caring for only infected or PUI patients. If neither option was available, the Centers for Disease Control and Prevention (CDC) advised treating such patients at the end of a row or in a corner of the dialysis facility separated from noninfected patients by at least 6 ft. Most dialysis centers adopted policies for patients to phone in before arrival if they had symptoms suggestive of infection. Patients are screened on arrival with temperature measurement and screening questions about symptoms and possible exposure. Waiting rooms are largely unused, and patients are asked to remain in their cars when possible and come directly to the dialysis station when it is ready for their arrival. Any patients who screen positive are separated from all others.

The timing of the safe return of patients to the dialysis center after SARS-CoV-2 infection symptoms are gone remains a challenge. Widespread limits on availability of reverse transcriptase-polymerase chain reaction (rt-PCR) testing for COVID-19 made it difficult to decide when patients are no longer shedding virus or viral particles. CDC guidance suggested that infected patients who have recovered from the symptoms of COVID-19 may return to the general dialysis population after two negative rt-PCR tests separated by at least 48 hours. An alternative time-based strategy permitted return 10–20 days after a positive test in the absence of symptoms. However, dialysis patients recovering from COVID-19 often continue to have positive tests for weeks or even months. Since the presence of detectable viral RNA does not necessarily indicate infectivity, these patients with persistently positive rt-PCR created confusion in this vulnerable population. While patients with normal kidney function recovering from COVID-19 are no longer infective 9–10 days after symptoms first appear, even if they have detectable viral RNA in their nasopharynx, it is not clear that the same can be said for dialysis patients, many of whom have impaired immune response systems. For this reason, the CDC eliminated its suggestion for postinfection viral testing and now advises using only the time-based method to determine when recovered patients can return to the general dialysis population. Antibody tests indicate prior exposure to the virus, but their exact meaning is not yet clear. Although some antibody tests are positive in 15%–20% of patients without known COVID-19 infection, the high prevalence of asymptomatic infection makes it difficult to interpret this finding. Vaccines against SARS-CoV-2 are expected to be widely available in 2021. Given the impact of COVID-19 on patients with CKD, it is essential that their safety and efficacy be tested in this population. Once vaccines are proven safe and effective, patients with CKD and those caring for them must be given priority for vaccination.

Anxiety and emotional stress increased in dialysis patients during the COVID-19 pandemic. All dialysis patients, those infected, and those fearing infection may suffer from debilitating psychological distress. Tools to manage these symptoms include individual counseling and group sessions using electronic communication tools. Creative solutions, such as telehealth visits from social workers, dieticians, and for many needs, physicians, were used in outpatient dialysis centers. A waiver from the Centers for Medicare and Medicaid Services (CMS) during the public health emergency (PHE) permitted use of telehealth for monthly capitation visits. Telehealth may also be useful for patient and family education about home dialysis and transplant options and initial evaluations.

Because of the large number of patients suffering a critical illness as a result of acute respiratory distress syndrome (ARDS) associated with COVID-19 infections, attention turned to potential shortages of life-sustaining equipment like ventilators. While increasing the supply of available ventilators was the first priority, serious discussions were held about rationing them if the patient need exceeded the available supply. Policymakers considered guidelines for allocating ventilators; the State of Alabama Emergency Operations Plan stated that patients with end-stage organ failure, including anyone requiring dialysis, not receive ventilator support. The U.S. Department of Health and Human Services (HHS) Office of Civil Rights resolved a compliance review, and a revision removed this guideline. Recommendations are for a nuanced approach to rationing limited resources without arbitrarily excluding individuals.

Staff

Dedicated professionals care for patients with CKD every day; the COVID-19 pandemic changed the paradigm dramatically. Dialysis nurses and technicians are the major heroes, daily caring for in-center patients despite the risk to themselves and their families. Other staff, including physicians, social workers, dieticians, and administrators, were encouraged to have less direct patient contact and use telemedicine or telephonic contact in some instances. Strict use of hand hygiene and personal protective equipment (PPE), including gloves, masks, gowns, and eye-protective shields or goggles, proved effective in preventing viral transmission. Early pandemic reports from Europe of viral spread among patients and between staff and patients were largely eliminated after widespread measures were used to detect infection and isolate PUIs. As some staff became ill and had to stay away on sick leave, the higher workload on those remaining was particularly stressful with the restrictions imposed by screening and PPE procedures. These critical staff who remain often are faced with a very difficult decision: to accept the risk of exposing themselves and their loved ones to a potentially fatal illness or to risk loss of salary and benefits and the psychological stress of turning away from critical needs if they decide to leave work. This dilemma places stress and anxiety on all staff and their families. Staff needs to be wary of subtle signs of COVID-19 infection while at the same time helping patients manage their physical and emotional symptoms. Staff had to learn to employ PPE and conduct their routine activities while attired with face shields, masks, gloves changed frequently, and isolation gowns.

At the same time, community-wide recognition of the valuable contributions of health care workers and enhanced relationships with colleagues and patients empowered those who worked through the pandemic. Many have shared that their self-value and confidence and pride blossomed during the pandemic, providing an opportunity to give to their community as never before. While some staff have elected early retirement, we believe that many young people may be inspired by staff heroism to choose health care professions.