Serological Testing for COVID-19 (SARS-CoV-2) in ESKD

A Comparative Study of Symptom-driven Surveillance vs. Cross-sectional Serological Screening of SARS-CoV-2 Infection of Patients With End-stage Kidney Disease Receiving Renal Replacement Therapy

Starting in late 2019, the world is facing a pandemic with the SARS-CoV-2 virus. Patients with end-stage kidney disease and on treatment with renal replacement therapy are high risk patients, as they are unable to maximize social distancing.

We plan to gather epidemiological data using two different diagnostic approaches. We will compare a symptom-driven screening, in combination with a nasopharyngeal swab plus computed tomography (clinical approach) against serological surveillance.

Study Overview

• Status: Completed
• Conditions: SARS-CoV 2; End Stage Renal Failure on Dialysis
• Intervention / Treatment: Other: dialysis

Detailed Description

In late 2019, a cluster of patients with unexplained pneumonia was linked to a novel beta-coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1. The world health organization subsequently has coined this disease as COVID-19. By the time the scientific community was alerted, the epidemiological data suggested that the virus had already spread to other regions of mainland China, as well as foreign cities with close transport links to the original epicenter 2. The world initially answered by divergent responses. Two months on, we are experiencing a devastating pandemic with local outbreaks across all continents.

As more and more patients arrive at the hospitals, our focus is drawn to the acute and the important issues, treating large numbers of patients in grave condition. The surge in patients requiring medical care may overwhelm even the most sophisticated healthcare systems 3. The approach adopted by almost all nations is to 'flatten the curve', i.e. to reduce peak demand of healthcare resources 4. While individual countries follow different paths, the common denominator is to maximize social distancing. The main goal is to reduce the basic reproduction number (R0) as much as possible, to ideally less than 1.

An overview of the clinical characteristics of confirmed cases in China alerted the world that young age does not protect against infection 5. Disease severity, however, varies by age with more elderly people becoming seriously ill, and by underlying medical condition(s) 6. The impact on peak medical demand thus will be even greater if we succeed in maximizing social distancing of the most vulnerable and most frail patients, those who are more likely to become seriously ill.

This is, however, difficult for dialysis patients who cannot self-isolate and cannot avoid multiple contacts per week with health care workers and other patients. While isolating dialysis patients and health care workers with a suspected SARS-CoV-2 infection is important to limit transmission of the virus, these measures are insufficient to avoid transmission since it is estimated that asymptomatic or paucisymptomatic people play a major role in the spread of the virus. So far, epidemiological data in patients on IHD during an SARS-CoV-2 outbreak are limited. A single case-series of cases from China has been reported in prepublication. 37 out of 230 patients were infected with SARS-CoV-2, of which 6 died (crude mortality rate 16.2%). The authors suggest that not all of these died directly from the consequences of COVID-19. However, adjudication of cause of death might differ in future case series.

The current gold standard for the diagnosis of acute respiratory syndrome due to SARS-CoV-2 (COVID-19) is the detection of viral RNA in respiratory tract samples. The sensitivity of a negative PCR result is, however, not 100%. False-negatives can occur, especially when using nasopharyngeal swabs (positivity rate estimated at 54%-74%) due to sampling error and in patients with low viral loads, especially in patients who present at day 8 or later and mild cases. While a CT scan can be a valuable tool in patients with a suspicion of COVID-9, measurement of antibodies against SARS-CoV-2 is the only reliable way to estimate the prevalence of SARS-CoV-2 infection since patients can be pauci-symptomatic or asymptomatic.

A number questions remain regarding the use of antibodies for epidemiologic studies and to determine immunity. Can someone have a colonization with SARS-CoV-2 without developing IgG antibodies? In this case, would this person be protected against reinfection? Doctors of the University of Bonn recently reported on April 9th (H. Streeck et al.,data not yet published) that only 15% of a sample of 1.000 inhabitants of the small town Gangelt, a local hotspot in North Rhine Westphalia tested positive for IgG antibodies. These data suggest that even in severely affected regions the critical threshold for herd immunity might not have been reached. This means that there is a significant risk of new outbreaks, particularly after schools might reopen later (maybe in summer 2020, and in fall 2020).

Given that dialysis patients are at the same time potentially more vulnerable to SARS-CoV-2 infection, and cannot self-isolate, it is important to closely monitor this group of patients. A second benefit of this population is that it easily accessible for blood sampling, and close clinical follow-up is ensured.

The aim of this study is to determine the prevalence of patients who were infected with SARS-CoV-2 by measuring IgG antibodies at different time points.

Trial objectives The aim of the current study is to collect epidemiological data of the incidence of severe acute respiratory syndrome Corona Virus type 2 (SARS-CoV-2) infections patients with end-stage kidney disease in a Belgian Hospital setting.

The objective is to compare two means of detection of infection, one symptom-driven surveillance and a second based on cross-sectional serology.

Primary endpoints Positive serology for SARS-CoV-2 at census date(s)

Secondary endpoints Detection of SARS-CoV-2 infection by symptom-driven surveillance

Trial Design Cross-sectional and longitudinal observational study of prevalent patients with end-stage kidney disease

• Study Type: Observational
• Enrollment (Actual): 500

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University Hospitals Leuven
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Jessa Ziekenhuis
    • Sint-Truiden, Limburg, Belgium, 3800
      • Sint Trudo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with end-stage kidney disease (ESKD) receiving renal replacement therapy

Description

Inclusion Criteria:

• Patients with end-stage kidney disease (ESKD) receiving renal replacement therapy
• Age 18 years or older
• Treated at University Hospitals Leuven, or Jessa Ziekenhuis Hasselt
• Providing informed consent

Exclusion Criteria:

• Refusal to provide informed consent
• Transfer to another dialysis unit

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ESKD; Patients with ESKD and on treatment with any form of dialysis	Other: dialysis; treatment with dialysis. This can be hemodialysis, hemodiafiltration, peritoneal dialysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibodies against SARS-CoV-2	serology to test for IgG and IgM antibodies against SARS-CoV-2	one year

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Bjorn Meijers, MD, PhD, UZ Leuven

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2020
• Primary Completion (Actual): December 12, 2022
• Study Completion (Actual): December 12, 2022

Study Registration Dates

• First Submitted: May 5, 2020
• First Submitted That Met QC Criteria: May 6, 2020
• First Posted (Actual): May 7, 2020

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 1, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: serology; Chest CT; nasopharyngeal swab
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: S64000

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No