key: cord-1054647-yxbnr9m9
authors: Naljayan, Mihran; Yazdi, Farshid; Struthers, Sarah; Sharshir, Moh’d; Williamson, Amanda; Simon, Eric E.
title: COVID-19 in New Orleans: A Nephrology Clinical and Education Perspective and Lessons Learned
date: 2020-12-02
journal: Kidney Med
DOI: 10.1016/j.xkme.2020.09.012
sha: e36930a10b1c115eee576f9b37a1aa14718104d1
doc_id: 1054647
cord_uid: yxbnr9m9

New Orleans’ first case of COVID-19 was reported on March 9, 2020 with a subsequent rapid rise in the number of cases throughout the state of Louisiana. Traditional educational efforts were no longer viable with social distancing and stay-at-home orders, therefore virtual didactics were integrated into our curriculum. Due to an exponential increase in the number of patients with acute kidney injury requiring kidney replacement therapy, the nephrology sections at Louisiana State University School of Medicine and Tulane University School of Medicine adapted their clinical workflows to accommodate these increased clinical volumes by utilizing prolonged intermittent kidney replacement therapies and acute peritoneal dialysis as well as other strategies to mitigate nursing burnout and decrease scarce resource utilization. Telehealth was implemented in outpatient clinics and dialysis units to protect vulnerable patients with kidney disease while maintaining access to care. Lessons learned from this pandemic and subsequent response may be utilized for future responses in similar situations.

New Orleans' first case of COVID-19 was reported on March 9 th , 2020, approximately two weeks after Mardi Gras festivities culminated on February 25 th . This has led to speculation that Mardi Gras greatly accelerated what would become an explosive outbreak of COVID-19 in the New Orleans area. 1 Within weeks, most of the city's restaurants and bars shuttered their doors, effectively shutting down the tourism and hospitality industry upon which the local economy depends.

By the time Governor John Bel Edwards issued a statewide stay-at-home order on March 23 rd , Louisiana had over 1,000 confirmed cases of COVID-19 with one of the highest per capita infection rates in the nation. 2 Less than two weeks later, on April 3 rd , the number of cases had risen to over 10,000. With over two-thirds of cases occurring in the New Orleans area, our local healthcare system became inundated with acutely ill patients. 3, 4 In an unprecedented response effort, healthcare providers from all backgrounds worked collaboratively to care for patients under extremely challenging and often bleak circumstances. Those of us working in nephrology faced the dual challenge of increasing our surge capacity to meet the demands for kidney replacement therapy (KRT) in the inpatient setting while simultaneously implementing measures in the outpatient dialysis setting to ensure the safety of patients and staff.

In many ways, COVID-19 has been a uniquely deadly disease for the New Orleans area which at one point had the highest per capita death rate in the United States. 2 Certainly, our nephrology experience has been that kidney involvement from COVID-19 is associated with increased mortality, particularly when KRT is required. 5 But we would also support the observation made in the broader medical community that J o u r n a l P r e -p r o o f 3 racial and social disparities have played a significant role in disproportionate mortality rates, in New Orleans in particular. 6 This resounds from our prior experience with Hurricane Katrina in which socioeconomic risk factors led to increased vulnerability for poor outcomes. 7 While we collectively work to eradicate these disparities, we must ensure that they are properly addressed in future pandemic and disaster response plans to improve outcomes for vulnerable populations.

The following review details our experience dealing with COVID-19 in our two academic medical centers in New Orleans in regards to our educational and clinical experiences. Lessons learned from this pandemic and subsequent response may be utilized for future responses and in other geographic areas who experience a similar situation.

The COVID-19 pandemic has required a major restructuring of both clinical and educational efforts within our respective nephrology departments. As reports emerged of COVID-19 spreading throughout the U.S., both LSU and Tulane medical schools enforced a mandatory quarantine period for individuals traveling from parts of Asia back to New Orleans. One faculty member at LSU was required to quarantine for 14 days upon arrival to the U.S. which necessitated urgent rearrangement of the faculty schedule.

Additionally, several fellows required sick leave due to suspected or confirmed SARS-CoV-2 infection. In order to maintain sufficient inpatient service coverage, outpatient duties for both faculty and fellows were minimized to the extent possible, including clinics and dialysis rounds.

With more time spent on inpatient services as well up to 80% increase (generally 15-20 patients increased to 35-45 patients) in the number of nephrology consults across our institutions, there was significant concern for burnout in both faculty and fellows.

Based on prior studies showing that courses in mindfulness-based stress reduction decrease clinician burnout, we introduced wellness and mindfulness sessions into our weekly didactic conferences and also held weekly Zoom™ check-ins with fellows to ensure their concerns were heard and addressed. 8 One such session included a clinical psychologist from LSU School of Medicine educating the section on breathing exercises to decrease stress. After meeting with internal medicine residency leadership, we were able to recruit additional residents to assist fellows on the consult services. We also doubled our weekend inpatient coverage to include two fellows and two attendings where needed in order to reduce workload. As the censuses increased across hospitals, faculty and fellows spent additional hours providing care to patients. The rotation structure and call schedule was otherwise unchanged.

With regards to educational efforts, all didactic sessions were transitioned into web-based audiovisual meetings using the Zoom™ platform. The originally planned curriculum largely remained unchanged in order to minimize disruption in content delivery. With most of our inpatient consults being related to COVID-19, both fellows and faculty welcomed the opportunity to learn and teach about traditional nephrology topics.

Due to all medical students being dismissed from clinical services, three students who had previously been assigned to nephrology consult services or clinics no longer had the ability to experience nephrology. Knowing that students who are not exposed to J o u r n a l P r e -p r o o f nephrology are less likely to choose nephrology as a career, we implemented Zoom™ on inpatient rounds and in telehealth clinics so that students could engage with the team virtually. 9 Prior to rounds on the consult service, students were assigned patients to perform chart reviews, and they presented those patients during rounds virtually to the team with a laptop that included webcam videoconference ability. The students were able to discuss the results of diagnostic tests as well as review assessments and plans with the fellow and attending. Although they were unable to do physical exams, this still offered students the ability to participate in learning during their nephrology consult service block.

The factors for developing acute kidney injury (AKI) with SARS-CoV-2 infection vary by region. Reports from China indicate a very low incidence of elevated creatinine or chronic kidney disease (CKD) while elsewhere the incidence is much higher-as high as 47% in the U.S. 10 In all reports, baseline elevation in creatinine was associated with a higher incidence AKI. The overall incidence of AKI is reported to be 37% in the US with of ventilated patients receiving dialysis died. The presence of AKI severe enough to require dialysis is often seen in the setting of multisystem organ failure and "cytokine storm" which may not always be the case for ESKD patients. Our results in New Orleans support underlying CKD as a risk factor for AKI, need for KRT, and increased mortality.

The etiology of AKI in COVID-19 appears to be multifactorial. As with any infection, acute tubular necrosis is prominent. However, there is also prominent interstitial infiltration of lymphocytes and macrophages. 12 Interestingly, the C5b-9 (the membrane attack-complex of the alternate complement pathway) has been seen on tubules in autopsy specimens. 13 The alternate complement pathway has been noted in SARS and a trial of eculizumab is under way in ARDS with COVID-19. 14 The kidney expresses the receptor for SARS-CoV-2 , the angiotensin converting enzyme 2 (ACE2) is present on the proximal tubule brush border and glomeruli. 15 However, how the virus would gain entry from the tubule luminal side is unknown as is the mechanism of J o u r n a l P r e -p r o o f necessary virus cleavage (a process known as priming) though the enzyme furin (but not the TMPRSS2) is present. 16 SARS-CoV-2 virions have been found in kidney tubules and podocytes, 12 though this has been questioned. 17, 18 Viral RNA has also been detected in the proximal tubule. 19 This has generated the hypothesis that direct toxicity of the virus on kidney tubule cells is important. Other studies suggest a podocytopathy. In a case report from our institution, a patient developed nephrotic range proteinuria and fairly new onset of severe AKI. 20 The biopsy showed collapsing focal and segmental glomerulosclerosis and was homozygous for an APOl-1 risk allele. Subsequently the patient's COVID-19 nasopharyngeal swab was positive. This raises the possibility that COVID-19, like HIV, can be the "second hit" that triggers FSGS in susceptible patients. 21, 22 Other factors proposed in the etiology of COVID-19 AKI include tissue hypoxia, coagulopathy and rhabdomyolysis 12 ; we have also anecdotally observed rhabdomyolysis.

During the course of the pandemic, nearly all hospitals in the New Orleans area saw a tremendous surge in the demand for KRT for both patients with AKI and ESKD.

When comparing data between March 15, 2020 to April 15, 2020 to the same period in 2019, there was a 47.3% total increase in inpatient dialysis treatments across the city, including a 261.5% increase in continuous KRT treatments and 7.4% increase in peritoneal dialysis (PD) treatments.

In anticipation of this surge, early attempts to increase capacity included spacing out intermittent hemodialysis (HD) treatments in ESKD patients with significant residual J o u r n a l P r e -p r o o f kidney function, shortening treatment times to 2-3 hours, and facilitating discharge to outpatient facilities when medically appropriate.

Initially, all persons under investigation (PUI) and confirmed positive patients were treated in a 1:1 isolation setting requiring acute HD nurses to spend many hours performing these treatments. A 71.1% increase in 1:1 HD treatments was seen during the time frame noted above. Eventually, due to the inability to keep up with the demand of 1:1 HD treatments, both AKI and ESKD patients requiring HD with confirmed COVID-19 were cohorted to the last shift of the day following regular and PUI shifts. Droplet precautions were maintained in the dialysis unit and staff wore full PPE according to CDC recommendations.

UMCNO also provides dialysis services for undocumented immigrants and some other uninsured patients who come to the emergency room. During the surge, this placed an added burden on the already stressed hospital dialysis unit. This also led to the concern of exposure to SARS-CoV-2 for those patients who were dialyzing in the hospital acute unit.

Providing KRT to COVID-19 patients in the ICU has been challenging. With our first cases of AKI requiring KRT, it became clear that our standard therapy of continuous veno-venous hemodialysis (CVVHD) would not be sustainable for two main reasons.

First, the hypercoagulability that has been widely observed in COVID-19 infection led to such excessive clotting of hemofilters that it was impossible to keep patients on dialysis long enough to provide a therapeutic benefit. Second, we could not meet the clinical demand for KRT by running our six NxStage™ machines continuously for each patient J o u r n a l P r e -p r o o f (Table 1) . After clotting persisted despite a trial of a systemic heparinization, CVVHD was abandoned for a period of time in favor of intermittent HD with vasopressor support.

While this significantly reduced both time spent at the bedside and PPE usage for ICU nursing staff, it also led to suboptimal volume management in some patients who had significant obligate intake. It also imposed a significant burden on our HD nurses given the large numbers of patients needing 1:1 HD. Following the release of American Society of Nephrology (ASN) guidelines on March 21 st for management of KRT in hospitalized patients, prolonged intermittent KRT was suggested for select ICU patients. 23 By utilizing a combination of prolonged intermittent KRT and HD modalities, with HD reserved for the more hemodynamically stable patients, we were able to provide KRT to more patients on a daily basis. We also noted significantly less clotting with prolonged intermittent KRT due to use of higher blood flows in conjunction with systemic heparinization.

As COVID-19 cases increased, the demand for intermittent HD and continuous KRT outpaced our ability to continue supplying those therapies. For this reason, alternative strategies such as using acute PD for AKI were implemented in the hospital. A number of studies from Brazil and Saudi Arabia showed acceptable rates of clearance and ultrafiltration using acute PD to treat AKI. [24] [25] [26] The LSU Acute PD protocol was developed, implemented and distributed amongst nephrologists around the New Orleans metropolitan area using the guidelines of the International Society of Peritoneal Dialysis (ISPD). 27 A surgeon or interventional radiologist was identified at each hospital with experience in placing PD catheters. Rather than placing PD catheters in the operating J o u r n a l P r e -p r o o f room, surgeons placed PD catheters at the bedside in the ICU on ventilated patients using a bedside mini-laparotomy technique with cut-down to rectus muscle and subsequent tunneling of the catheter. Patient selection was another factor to initiate acute PD.

Patients who were mechanically ventilated and required prone positioning were considered poor candidates for acute PD though has been reported previously. 28 Patients with acute abdominal infection, severe hyperkalemia, severe volume overload or a history of extensive abdominal surgery were also considered poor candidates. Using low dwell volumes in the supine position, automated cycler PD was initiated. ICU patients received 24 hours of therapy whereas patients on the ward received 12 hours of therapy.

Ultimately, 13 patients utilized acute PD for AKI.

As New Orleans was one of the first cities in the U.S. to experience an outbreak of COVID-19, we had to improvise prior to the large dialysis organizations (LDOs) providing significant guidance. Similar to the strategies employed by colleagues in Seattle 29 , we began by screening patients for symptoms and isolating or cohorting them within their usual dialysis shift. Subsequently, upon recommendations from one LDO, one dialysis unit was designated to provide dialysis services for all PUI patients and another unit for all confirmed COVID-19 patients, each on separate shifts that had previously been open. At another LDO, one shift was identified to dialyze all PUI as well as confirmed patients, moving all other patients to other shifts. Regardless, neither plan was ideal because of the potential for PUIs and positives to be mixed prior to the advent of rapid testing. Since rapid testing has been made available, we have been able to isolate and dialyze a PUI and by the next treatment know their actual COVID-19 status.

With regards to patients on home modalities, we felt a duty to keep them safe at home without the need for unnecessary exposure. Within one week of the first COVID-19 case in Louisiana, we implemented telehealth visits with approximately 80% of our home dialysis patients. We were able to consolidate all dialysis unit visits (for lab draws, adequacy and medication administration) to one visit per month and have been successful in maintaining this frequency of visits. These lead to minimal SARS-CoV-2 exposure for our home dialysis patients.

Patients with CKD were also transitioned to telehealth. Routine visits for CKD stages 1-3 were largely postponed after a phone call to check in with them. Patients with more advanced CKD or issues requiring more urgent evaluation were scheduled for either a telehealth visit or in-person visit according to their preference. Parishes began seeing evidence of a plateauing of cases by April 15. The daily death rate rapidly increased in the initial period after the first positive patient was identified, with a downward trend over the next few weeks, but a small increase as a second peak of deaths occurred ( Figure 1 ). Concurrent with the daily death rate, we also saw a rapid increase in hospitalized patients followed by a downward trend with a second, smaller peak.

Mechanical ventilation followed a similar trend but the second peak was much flatter ( Figure 2 ).

It would be an understatement to describe this COVID-19 pandemic as anything short of the most significant event to involve the medical community in over a generation. Likewise, our experience within the nephrology community has been extremely challenging. The notion that dialysis is an essential service and requires patients to frequently trust us by risking exposure to the virus is not to be taken lightly;

we have a responsibility to ensure the safety of our patients on maintenance dialysis and J o u r n a l P r e -p r o o f avoid hospitalizations. The surge of incident acute kidney injury episodes within our institutions was a burden on our resources, and this required frequent communication between institutions and services. There were many changes and disruptions to an academic program, including transitioning conferences to a virtual format, cancelling other conferences outright, COVID-19 illness amongst our trainees and the need to make concessions to avoid burnout due to coverage and patient load (Figure 3) . Ultimately, what allowed us to sustain our practice within this first wave of virus cases was the state's order for Louisianans to stay at home, social distancing, better sanitation and the work of the Louisiana Department of Health. There are still yet many unknowns but we must find opportunities in this lull to start answering them.

Authors' Full Names and Academic Degrees: Mihran Naljayan, MD 1 

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